Alzheimers Archives - First Washington News

February 28, 2023

Obesity linked to 21 genes related to Alzheimer’s disease, study finds

The World Overall health Business estimates that around 55 million men and women worldwide have dementia, with Alzheimer’s disorder currently being the most typical kind of the ailment.
Weight problems is a regarded modifiable possibility component for this kind of dementia.
Scientists from The College of Texas Health and fitness Science Middle at San Antonio uncovered 21 of 74 recognised Alzheimer’s-related genes are also connected to weight problems.

In accordance to the Entire world Overall health Firm (WHO), extra than 55 million people today have dementia.

Weight problems is a regarded modifiable risk element for Alzheimer’s ailment — a kind of dementia impacting an approximated 32 million persons globally.

In addition, researchers from The University of Texas Overall health Science Middle at San Antonio have found 21 of 74 known genes linked to Alzheimer’s sickness are also connected to obesity. Experts consider this might assistance reveal why adults who expertise weight problems in midlife a lot more regularly acquire Alzheimer’s illness.

The examine appears in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Obesity is a ailment affecting the entire overall body and its well being. A man or woman is overweight if their pounds is increased than what is usually considered healthier for their peak, also known as their body mass index (BMI).

Preceding investigate suggests that sustaining an ideal BMI for height may well help minimize the chance for Alzheimer’s condition. Moreover, a current analyze found the style of neurodegeneration brought about by obesity is very similar to the kind leading to Alzheimer’s disorder, suggesting that managing bodyweight could help slow cognitive decrease and decrease a person’s possibility for Alzheimer’s.

Previous exploration reveals obesity causes swelling in the entire body, which can direct to not only an elevated hazard for Alzheimer’s but other conditions which includes cardiovascular disorder, diabetes, and stroke.

In accordance to Dr. Claudia Satizabal, assistant professor at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Ailments and The University of Texas Health Science Center at San Antonio and the study’s corresponding writer, the crew made a decision to look for a genetic connection involving being overweight and Alzheimer’s disease because, from preceding scientific studies, we know that weight problems — significantly in midlife — is a hazard component for Alzheimer’s sickness dementia, but we do not absolutely recognize why.

“Thus, we requested the problem, what if being overweight modifications the expression of important genes implicated in Alzheimer’s that could help make clear some of the mechanisms linking these two problems?” she told Health-related News Now.

For this analyze, Dr. Satizabal and her workforce analyzed 74 Alzheimer’s-relevant genes from in excess of 5,600 members of the Framingham Coronary heart Analyze.

Upon examination, scientists identified of these 74 genes, 21 were possibly beneath-expressed or in excess of-expressed in obesity. Furthermore, scientists observed 13 Alzheimer’s-connected genes ended up related with BMI, and 8 were being connected to waistline-to-hip ratio.

“We ended up expecting some associations simply because recent genetic research of Alzheimer’s dementia have pointed to genes concerned in the metabolism of lipids and the immune program, both equally of which can be dysregulated in being overweight,” Dr. Satizabal stated. “However, we ended up a minimal stunned to see as many — the expression of just about 30{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of the Alzheimer’s illness genes showed back links with weight problems features.”

Dr. Satizabal mentioned despite the fact that they can’t derive fast suggestions for individuals from this analyze, these results insert to the developing literature linking obesity and Alzheimer’s dementia.

“It is important to explore with clients the implications of extra pounds, specially belly weight problems, to maintain cardiovascular and brain wellness as we age,” she included.

Scientists pointed out this study’s limitation as most data from the Framingham Coronary heart Study was from a generally white population.

“We imagine the associations concerning Alzheimer’s-associated genes and obesity could be even extra appropriate in Hispanics, who have a higher prevalence of being overweight, but that is however to be examined,” Satizabal states. “We need to raise the sampling of varied populations to come across more genetic markers linked to dementia.”

As for the future measures in this investigation, Dr. Satizabal stated, “We are preparing to replicate these conclusions in further, more numerous samples, and adhere to up on vital mobile and molecular mechanisms.”

Healthcare Information Currently also spoke about this review with Dr. Santosh Kesari, a neurologist at Providence Saint John’s Overall health Centre in Santa Monica, CA and regional health care director for the Research Medical Institute of Providence Southern California.

He stated he was not stunned by the study’s findings because we know continual diseases these types of as being overweight cause all kinds of challenges, such as dementia.

“It was attention-grabbing to come across which genes, but at the exact same time it was not completely astonishing that there would be a established of genes that could demonstrate the hazard of neurodegenerative diseases in individuals with weight problems,” he extra.

When questioned what the correlation involving being overweight and Alzheimer’s sickness may well be, Dr. Kesari mentioned we do not nevertheless know the entire tale.

“It would seem some of the story is in this new publication for the reason that some of the genes concerned that are similar to weight problems and enhanced danger of Alzheimer’s in this dataset spotlight the job of neuroinflammation,” he ongoing. “At minimum a several of the genes are linked. We know obesity triggers inflammation and some of those people similar genes seem to be implicated in neuroinflammation, which we feel is a single of the fundamental mechanisms of dementia, like Alzheimer’s dementia.”

For people today at large possibility for Alzheimer’s sickness, Dr. Kesari reported the before they can start preventive measures, the greater.

“If you have the genetic danger for Alzheimer’s, you know that in your 40s or 30s, you commence to transform your lifestyle and practices to avert troubles happening many years down the line,” he described. “And if being overweight is one particular challenge that also is connected to Alzheimer’s, undoubtedly cutting down body weight in your 30s and 40s will minimize the chance of dementia decades afterwards.”

“For disorders this kind of as Alzheimer’s, figuring out your chance and what you can do decades in advance of is heading to be the greatest action to avoiding it,” Dr. Kesari added. “Once you have dementia when you are obese, clearly [weight] reduction is nevertheless critical for your standard health, but it could not make substantially big difference in conditions of dementia that is already set in. These reports need to have to be finished as perfectly.”

October 28, 2022

‘Love hormone’ oxytocin may improve cognitive decline in Alzheimer’s

An elderly man and woman kiss under an umbrella to correspond to an article about dementia and the love hormone. — A new examine discovered that a derivative of oxytocin delivered by means of nasal passages enhanced memory in cognitively impaired mice. Laurence Monneret/Getty Pictures

Alzheimer’s illness is a frequent sort of dementia characterised by cognitive impairments and behavioral changes.
Latest cure alternatives for Alzheimer’s are confined to drugs that assist regulate the signs or symptoms.
A new examine has identified that a spinoff of oxytocin, also acknowledged as the ‘love hormone,’ delivered via nasal passages improved memory in cognitively impaired mice.
The scientists counsel that their conclusions could guide to practical remedy choices for Alzheimer’s in the clinical environment.

According to a 2021 Alzheimer’s Affiliation report, estimates in the United States indicate that 6.2 million individuals age 65 and more mature are dwelling with Alzheimer’s illness (Ad). The report implies this selection could develop to 13.8 million by 2060 unless helpful prevention or treatment options emerge.

At the moment, the induce of Alzheimer’s condition is not completely recognized. However some investigation implies the accumulation of amyloid B peptides (AB) in the brain may well engage in a role in the improvement of the condition.

Nonetheless, according to a 2022 Nationwide Institute on Getting older (NIA) statement, Advert is a advanced dysfunction that might involve other cellular variations. In addition to AB accumulation, proteins which includes tau, TDP43, and alpha-synuclein might also be a variable. Furthermore, inflammation, genetics, environmental aspects, and vascular changes may well also enjoy a function.

Now, Alzheimer’s remedy possibilities are confined to prescription drugs that may well assist regulate cognitive and behavioral symptoms affiliated with the ailment.

Now, a new review by scientists at the Tokyo College of Science uncovered that a mobile-penetrating oxytocin by-product administered in the nasal passages of memory-impaired mice reversed the rodent’s cognitive impairment.

Whilst the study used mice and not human individuals, the conclusions advise that oxytocin could perhaps cut down the cognitive impairments connected with Alzheimer’s condition.

Oxytocin is a hormone responsible for bonding behaviors and intimate attachment. Hence, it is normally referred to as the “love hormone.” Oxytocin also plays a important part in childbirth and nursing.

In a past study by the Tokyo University of Science scientists, the experts located that oxytocin could reverse the consequences of amyloid-beta (Aβ) peptides in the hippocampus of mice.

Constructing on these conclusions, the investigate crew sought to take a look at the consequences of oxytocin in Aβ-induced memory-impaired mice.

Particularly, the researchers required to determine whether or not oxytocin would impact spatial memory.

1st, the researchers had the mice complete Y-maze and Morris water maze (MWM) checks to study spatial performing and spatial reference memory. The crew also evaluated the rodent’s locomotor action employing a multi-channel action-counting technique.

Then, in just one group of rodents, the team utilized intracerebroventricular (ICV) administration to deliver oxytocin to the mind tissue.

Mainly because of the ICV technique’s invasive nature and impracticality in a medical setting, the researchers also made use of intranasal (IN) shipping and delivery to administer oxytocin in a different group of mice.

According to the analyze, peptides like oxytocin have very poor blood-mind barrier permeability — that means they just can’t effortlessly enter mind tissue.

Hence, the staff used an oxytocin by-product containing mobile-penetrating peptides and a penetration-accelerating sequence for the nasal supply experiments.

In addition, the researchers labeled the spinoff with fluorescein isothiocyanate so they could see how it dispersed in the brain tissue with imaging tactics.

Soon after the oxytocin-dealt with mice carried out the spatial memory assessments, the researchers uncovered that the mice who gained oxytocin as a result of ICV administration showed advancements in memory in the two the Y-maze and MWM checks.

Mice that been given IN administration of the oxytocin by-product only showed memory advancements in the Y-maze check.

Even now, by observing the fluorescein isothiocyanate-labeled oxytocin, the scientists observed that the oxytocin derivative was dispersed during the rodent’s mind tissue immediately after IN administration.

According to the study authors, the effects counsel that IN supply of the oxytocin derivative effectively reaches mind tissue and could be a useful remedy for cognitive impairment in medical configurations.

“My workforce is the first to demonstrate that the oxytocin by-product can make improvements to [B-amyloid peptide]-induced memory impairment in mice,” examine senior writer Jun-Ichiro Oka, Ph.D., professor emeritus at the Tokyo University of Science, mentioned in a information release.

“This suggests that oxytocin may perhaps enable cut down the cognitive drop we see in Alzheimer’s disease.”

Just after reviewing the research, James Giordano, Ph.D., professor of neurology and Biochemistry at Georgetown University Healthcare Centre, Washington, not concerned in the research, explained to Medical New These days:

“This is an important paper in that it demonstrates a putative job for the neuropeptide oxytocin in both of those protecting and considerably restorative results against (amyloid-induced) neurodegeneration. Further more, it reveals that each endogenous oxytocin [and] exogenously administered oxytocin can exert this sort of outcomes in an animal product.”

“Interestingly, it is recognized that a associated neuropeptide, vasopressin, also contributes to memory formation and processing in the mammalian mind, and this analyze might get rid of new light on the interactive roles of neuropeptides in brain well being, safety versus oxidative stress, and in sustaining neurocognitive functions.”

– James Giordano, Ph.D., professor of neurology

Dr. Ajay Verma, Ph.D., a general partner with Development Venture Engineering and previous professor of neurology at the Uniformed Companies University of the Health and fitness Sciences, also not included in the analyze, instructed MNT:

“This exploration by Akiyoshi Saitoh’s group from the Tokyo College of Science could have implications for investigation in Alzheimer’s ailment, as well as brain drug shipping. These researchers have previously claimed useful effects of oxytocin on isolated brain tissue and now display this in a stay animal design of amyloid-induced memory dysfunction.”

“Delivering peptides this kind of as oxytocin to the brain is tough, and so these scientists labored on novel modifications to aid this shipping and delivery,” Dr. Verma said.

“Intranasal (IN) delivery of peptide prescription drugs has extensive been sought as a noninvasive route to the brain, and although this tactic generally operates perfectly in animals with long snouts, it has historically not translated perfectly to primates, such as humans. This examine exhibits that a modified edition of oxytocin with improved cell uptake was powerful in the memory decline model when presented by means of intranasal dosing, though the native variation of oxytocin was not.”

– Dr. Ajay Verma, Ph.D., neurologist

Dr. Verma additional that several drug mechanisms suggested by animal models have not translated into added benefits in medical trials.

“We will have to wait and see how this is translated in people,” he mentioned.

“However, this study also implies that certain peptide modifications may well assistance produce prescription drugs a lot more efficiently across the nasal-mind barrier, and this expertise could be utilized to increase mind delivery of numerous prescription drugs.”

Posted on July 7, 2022
Scientists spot gene that may explain why more women get Alzheimer’s

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Women are disproportionately affected by Alzheimer’s disease. Leonardo Laschera/EyeEm/Getty Images

Alzheimer’s disease (AD) affects nearly twice as many women as men.

About 60{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of people with AD don’t express apolipoprotein E (APOE ε4), its most established genetic risk factor.

New research has shown the MGMT gene may be associated with a higher risk of AD in two different populations, particularly in women without APOE ε4.

The study found that the expression of MGMT contributes to the development of toxic proteins associated with Alzheimer’s, especially in women.

AD is the most common form of dementia, a gradual condition that causes the brain to shrink and the cells to die. The condition affects a person’s ability to remember, think, and carry out simple tasks.

According to the Centers for Disease Control and Prevention (CDC), over 5.8 million people in the U.S. are living with AD and dementia, which is predicted to rise to nearly 14 million by 2060.

AD is caused by the toxic buildup of amyloid proteins around the brain cells and tau proteins inside the brain cells.

Genetic studies have linked AD risk to the gene APOE ε4, however, 60{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of people with AD do not carry the gene, suggesting that other genes may be involved in the condition.

A recent study suggests that a new gene could be linked to a higher risk of developing Alzheimer’s, particularly in women.

The study is published in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association.

According to the Alzheimers Association, women are nearly twice as likely to be affected by AD than men. This is thought to be due to them living longer.

“[..] women over 60 are twice as likely to develop Alzheimer’s disease, […] than they are to develop breast cancer during the rest of their lifetime,” explained Dr. Rosa Sancho, the head of research at Alzheimer’s Research, who was no involved in the study.

Researchers trying to understand these differences have shown changes in the tau gene (MAPT) region in women with breast cancer, people with AD without APOE ɛ4, and women with ovarian cancer.

In a new study using genome-wide sequencing (GWAS), researchers from the Boston University School of Medicine, University of Chicago, and the University of Pennsylvania, among others, found a gene called MGMT which may increase the risk of AD in women.

To understand if other genes involved in tau-related diseases are related to AD risk in women, the researchers performed GWAS on two different populations:

31 members of the Hutterites, a group of people with common ancestry, recognized for their relatively small gene pool, 22 of whom were women.

10,340 women without APOE ɛ4, who were part of the Alzheimers Disease Genetics Consortium (ADGC). These included 3,399 AD cases and 6,905 controls.

Researchers found that in both populations, the MGMT gene was associated with AD risk in women lacking APOE ɛ4.

“[..] The fact that studies with such different designs identified (different) genetic variants that were linked to the same gene was unexpected,” said Dr. Carole Ober, chair of human genetics at the University of Chicagoand joint study lead.

“The different lines of evidence supporting a role for MGMT in Alzheimer’s disease risk increased our confidence,” she said.

The work suggests that the expression of MGMT contributes to the development of toxic amyloid and tau proteins associated with the development of AD.

To understand the mechanisms behind the link, the researchers analyzed the brain tissue of 177 participants of the Framingham Heart Study, 58 with confirmed AD.

Speaking to Medical News Today about the mechanisms behind the findings, Dr. Ober explained:

“Our data suggest that the associated genetic variants affect levels of DNA methylation and/or other epigenetic marks, like open chromatin, and these epigenetic changes impact the expression of MGMT at key developmental stages […] is our current working hypothesis.”

“This research also highlights just how complex Alzheimer’s is, with the MGMT gene involved in a number of cellular processes that could contribute to the development of disease.”
— Dr. Rosa Sancho

According to Ober, the study’s take-home message is “[…] an Alzheimer’s disease gene may impart its risk effects only in females and that epigenetic remodeling in neurons may be an important mediator of this risk.”

The next steps, he says, “are to first directly show that the genetic variants are involved in this epigenetic remodeling and then study the downstream effects of the remodeling in cell models of neuron development.”

“It’s going to take a concerted and global effort to develop life changing treatments, but genetic discoveries like this are a step in the right direction,” noted Dr. Sancho when asked about the significance of the study.

“The more we understand about risk genes and how they affect the development of Alzheimer’s, the closer we can get to new treatment approaches for the disease.”
— Dr. Rosa Sancho

Dr. Jennifer Bramen, senior research scientist at Providence Saint John’s Health Center, who was also not involved in the study, echoed these thoughts.

“Future research may find that the MGMT variants identified by this work […] may potentially lead to the identification of new drug targets or biomarkers—all important in treating and researching Alzheimer’s disease,” she said.

Dr. Bramen went on to say that “Lifestyle factors like walking, regular aerobic exercise, eating a healthy diet filled with fresh produce […] will do a lot to prolong cognition. As at-risk women grow older and lose the brain protection provided by estrogen, it is even more important that they take care of their health.”

“The brain is not separate from the body. Physical health is brain health, and therefore highly impacts cognitive abilities,” she added.

Posted on March 2, 2022
10 health factors associated with Alzheimer’s risk

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A new analyze finds one-way links amongst wellness disorders and Alzheimer’s chance. OLI SCARFF/AFP by means of Getty Images

There is no efficient remedy for Alzheimer’s disease, but researchers hope to recognize early possibility aspects that medical doctors can target to prevent or sluggish its progress.

An observational study has now highlighted 10 professional medical ailments related with a diagnosis of Alzheimer’s illness up to 10 several years later.

The circumstances contain acknowledged possibility aspects for the disorder, these kinds of as depression and listening to reduction, and problems with no links to the disease, these kinds of as constipation.

The research does not expose no matter if these situations assistance trigger Alzheimer’s or are early signs and symptoms.

Persons with dementia working experience a progressive loss of their potential to remember, think, and connect correctly.

On the other hand, the alterations in the mind that are liable for dementia may start off many years before its consequences on cognition and habits come to be obvious.

The Planet Health and fitness Business (WHO) indicates that of the 55 million people throughout the world residing with dementia, 60–70{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} have Alzheimer’s condition.

Tries to produce an efficient treatment for Alzheimer’s have fulfilled with small good results. Researchers are progressively turning their notice to detecting the sickness early.

The vital to this tactic is to establish early, “modifiable” hazard variables that medical professionals can concentrate on with medicine or other interventions.

Researchers at the Paris Mind Institute in France have now discovered statistical associations in between 10 overall health ailments and a diagnosis of Alzheimer’s sickness up to 10 decades later on.

Main melancholy was the earliest ailment to be connected with a subsequent analysis of Alzheimer’s, appearing at least 9 many years in advance.

Other problems that the review linked to a afterwards prognosis of Alzheimer’s involved:

panic

constipation

abnormal fat reduction

a variety of arthritis termed cervical spondylosis

response to intense stress

listening to loss

rest issues

They also confirmed that falls and tiredness experienced hyperlinks to Alzheimer’s risk.

The subsequent move will be to identify no matter whether these problems assist trigger the condition or regardless of whether they are early indications of variations in the brain that are by now happening.

“Diseases like Alzheimer’s can commence in the mind up to 2 decades ahead of signs start off to display,” reported Katy Bray, Ph.D., instructed Clinical News These days. Dr. Bray is a public engagement manager at Alzheimer’s Study Uk and was not concerned in the research.

“It is tricky to know how these situations might lead to the improvement of the ailment or if they could also be pretty early symptoms,” Dr. Bray advised Healthcare News Today.

The study appears in The Lancet Electronic Overall health.

The scientists analyzed the key health care documents of 20,214 people today with Alzheimer’s disease in the United Kingdom and 19,458 folks with Alzheimer’s in France.

They compared every single person’s health-related records with a command matched for intercourse and age who had not been given a diagnosis of a progressive brain sickness through the 15-yr analyze period.

Out of the 123 health and fitness conditions they investigated, 10 had a statistically substantial affiliation with a analysis of Alzheimer’s disorder 2–10 years afterwards in France and the U.K.

Some of the ailments, this kind of as despair, hearing decline, and sleep issues, are by now recognised threat things for Alzheimer’s.

Even so, this examine was the initially to identify constipation as a doable possibility element. The hyperlink involving the two problems became obvious 7 several years ahead of the prognosis of Alzheimer’s.

Apparently, constipation is also affiliated with melancholy and is an founded early sign of other mind health conditions, such as Lewy-system dementia and Parkinson’s sickness.

“The connections manufactured permitted us to ensure regarded associations, this sort of as listening to challenges or despair, and other fewer-acknowledged factors or early indications, such as cervical spondylosis or constipation,” says Thomas Nedelec, Ph.D., the initially creator of the examine.

“The query stays as to no matter if the health and fitness issues encountered are possibility components, symptoms, or warning signals of the sickness,” he additional.

In their paper, the authors conclude:

“Our results make it attainable to product the feasible trajectories of possibility elements in the period of time previous the prognosis of Alzheimer’s sickness, supplying new insights into attainable home windows for prevention.”

The study had some notable limitations. For example, it was not able to just take other chance factors that lead to Alzheimer’s, together with schooling level, ethnicity, socioeconomic position, and genetics, into account.

“This study provides a prosperity of data to our knowing of mental problems, these kinds of as despair, as a possibility component for dementia,” stated Claire Sexton, Ph.D., director of scientific programs and outreach at the Alzheimer’s Affiliation in the United States, who was not associated in the examine.

Even so, she emphasized that for the reason that their review was observational, somewhat than a medical trial, for instance, the scientists were unable to create no matter whether despair helps cause Alzheimer’s.

“Just mainly because a person has despair does not indicate they will go on to produce Alzheimer’s,” Dr. Sexton instructed MNT.

“However, these details guidance the strategy that using treatment of one’s psychological wellbeing is exceptionally crucial for total effectively-currently being and perhaps cognitive overall health,” she extra.

One more recent research also located an association amongst mental well being conditions and dementia.

In 2020, the Lancet Fee on dementia additional 3 new modifiable danger factors: too much alcohol use, head injury, and air pollution to its present listing, which contains:

hypertension

cigarette smoking

weight problems

depression

actual physical inactivity

diabetic issues

The report concluded that modifying all the risk components that scientists have determined could reduce or delay dementia in up to 40{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of persons.

“While midlife is rising as a key time for dementia chance, it’s never ever way too early or as well late in life to get motion on mind health,” Dr. Bray told MNT.

“This contains not smoking, only ingesting in moderation, remaining mentally and bodily energetic, consuming a well balanced eating plan, and keeping cholesterol and blood tension stages in verify,” she said.

Posted on January 24, 2022
Alzheimer’s and severe COVID-19: Comparing brain damage markers

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Healthcare worker Demetra Ransom comforts a person with COVID-19 at United Memorial Medical Center in Houston, Texas, on December 4, 2020. MARK FELIX/Getty Images

A study demonstrated that participants hospitalized with COVID-19 experiencing neurological complications had higher levels of blood proteins or biomarkers associated with neurological damage than people with Alzheimer’s.

Increased biomarker levels correlated with COVID-19 severity, mortality risk, and the presence of neurological disorder.

Long-term follow-up is necessary to determine if biomarker elevation is associated with an increased risk of developing subsequent neurodegenerative disorders.

COVID-19, the disease that a SARS-CoV-2 infection causes, often brings on mild upper respiratory symptoms. However, some individuals may experience severe illness requiring hospitalization. This can occur due to pneumonia and lung damage causing respiratory failure.

In addition, neurological manifestations commonly occur in people hospitalized with COVID-19. Neurological disorders may include encephalopathy, seizures, stroke, encephalitis, Guillain-Barré syndrome, and acute demyelinating encephalomyelitis.

Researchers at NYU Grossman School of Medicine conducted a study that investigated whether people with COVID-19 experiencing new-onset neurological complications during hospitalization had elevated blood markers indicating neurological damage.

The investigators published study results in the journal Alzheimer’s and Dementia.

Dr. Thomas Wisniewski, M.D., a co-author of the study, professor of neurology, pathology, and psychiatry, and director of both the NYU Alzheimer’s Disease Research Center and the Center for Cognitive Neurology, spoke about the study in an MNT interview.

He explained: “It’s clear that the [SARS-CoV-2] virus has a propensity for inducing vascular damage, targeting in the endothelial cells, and causing disruption of the blood-brain barrier, as well as inducing generalized neuroinflammation. Cytokines like interleukin 6 and interleukin 1 are much elevated in [individuals with COVID-19], and these are cytokines that drive neurodegeneration and Alzheimer’s disease.”

Cytokines are proteins that help the body’s cells to communicate.

Dr. Wisniewski added, “In our study, we became interested in looking at these types of biomarkers, [since these biomarkers] are what we follow in our Alzheimer’s disease research center for looking at the progression of Alzheimer’s-related pathology and other neurodegenerative disorders.”

In an interview with MNT, Jennifer Bramen, Ph.D., a senior research scientist at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study, described the seven biomarkers the study measured:

Total tau and pTau181 are indicators of neuron damage. Their levels increase as AD progresses. In AD, abnormal proteins form tangles, blocking the communication between brain cells, she explained.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is an enzyme that breaks down unnecessary proteins in brain cells. Brain injury or neurodegenerative diseases such as AD cause levels of UCHL1 to increase.

Increased glial fibrillary acidic protein (GFAP) levels indicate damage to the glial cells. Glial cells help maintain the health of brain cells and the blood-brain barrier, which filters toxic substances.

Neurofilament light chain (NfL) measures damage to axons of myelinated neurons. The axon is the part of the neuron that conducts electricity, and myelin is the insulation surrounding the neuron.

Amyloid-β (Aβ) 40 and 42 are proteins that build up and cause the formation of amyloid plaques in AD, which disrupt brain cell function and communication.

Lastly, a person’s pTau181 to Aβ42 ratio may identify early stages of AD.

Investigators also attempted to determine the association of increased biomarkers with rates of discharge to home and in-hospital death rates.

To assess the level of injury, the researchers compared serum biomarker levels of a control group of participants who had “normal” cognition, mild cognitive impairment (MCI), and AD with the biomarkers of people during hospitalization with COVID-19 and new neurological findings.

Researchers conducted a retrospective analysis of participants enrolled in the Study of Neurologic and Psychiatric Events in Acute COVID-19 (SNaP Acute COVID study), which examined serum samples people gave during their hospitalization for COVID-19.

Dr. Wisniewski explained, “We specifically excluded patients who have a preexisting cognitive disorder, any sort of dementia, or mild cognitive impairment, [to prevent clouding of the results].”

The SNaP Acute COVID study was a prospective study of 4,491 participants conducted in four New York hospitals between March 10 and May 20 of 2020, which evaluated the development of new neurological events during acute COVID-19 hospitalization.

The non-COVID control group comprised blood samples from the NYU Alzheimer’s Disease Research Center clinical core cohort banked before January 1, 2020. This was the date of the first reported COVID-19 cases in New York City. The researchers used validated testing tools — version three of the Uniform Data Set and the Clinical Dementia Rating — to stratify the control participants into three subgroups: normal cognitive functioning, MCI, and AD.

The study measured blood markers using an ultrasensitive testing methodology called single-molecule array technology.

The COVID-19 group consisted of 251 participants with a median age of 71. This group was 63{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} male. There were 161 participants in the control group with a median age of 71. Participants in the control group were 35{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} male.

The most common neurological complications included toxic metabolic encephalopathy (TME) in 63{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of participants and brain injury due to reduced oxygen or blood flow in 46{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}.

The severity of COVID-19 correlated most strongly with total tau, pTau181, and NfL levels.

Higher GFAP and pTau181/Aβ-42 levels were associated with a significantly increased risk of death during hospitalization. Results showed that elevated levels of total tau, NfL, and GFAP corresponded to decreased discharge-to-home rates.

Those participants with COVID-19 who experienced new neurological events during hospitalization had significantly higher total tau, pTau181, NfL, and UCHL1, with the highest levels occurring in those with TME. The participants with COVID-19 had a 179{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} percent higher NfL, 73{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} higher GFAP, and 13{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} higher UCHL1 level than the AD group.

Dr. Wisniewski commented:

“In the study, we found very marked elevations of these seven biomarkers, indicating [the] significant presence of neurodegeneration, neuronal death, and gliosis. With marked neurodegeneration, neuroinflammation, and — at least at one time point — elevation of Alzheimer’s disease biomarkers, each […] correlated with the presence of neurological disease and the severity of infection as well as the outcome.”

Dr. Braman stated: “One limitation is that [the study] is only looking at hospitalized patients, so it’s still not clear if these biomarkers might be present in patients with less severe COVID-19 symptoms. Future research would be [needed] to understand how long lasting these effects are and how much they link up with actual cognitive deficits.”

Dr. Wisniewski agreed:

“We have been following these patients for 6 months and one year […] and there was the persistence of cognitive dysfunction [in up to 50{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of these folks]. Hence, it’s important to follow this up. [P]erhaps biomarker findings speak of an increased risk of subsequent neurodegenerative disorders in this population.”

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

Posted on October 12, 2021
Genetic link between COVID-19 and Alzheimer’s identified

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A new study finds a genetic bridge between Alzheimer’s and COVID-19. Nor Hasen/EyeEm/Getty Images

In a new study, scientists have identified a genetic link between the development of Alzheimer’s and severe COVID-19 outcomes.

The study also identifies the same immune system changes in both diseases.

Targeting specific “risk” genes could lead to future treatments for Alzheimer’s disease and COVID-19.

Alzheimer’s disease is the most common form of dementia, a syndrome where cognitive function declines progressively over time.

According to the World Health Organization (WHO), over 55 million people live with dementia worldwide, and doctors diagnose 10 million new cases each year. Around 60–70{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of these are Alzheimer’s cases.

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“While Alzheimer’s is primarily characterized by a harmful buildup of amyloid protein and tangles in the brain, there is also extensive inflammation in the brain that highlights the importance of the immune system in Alzheimer’s,” explains Dr. Dervis Salih.

Dr. Salih is a senior research associate in neurodegenerative disease at University College London (UCL).

In previous work by UCL, genetic studies revealed that different genes can alter the risk of developing Alzheimer’s disease. These “risk genes” change how microglia, or immune cells of the brain, respond to amyloid protein and tangles.

Scientists have focused on a subpopulation of microglia cells known as interferon response microglia (IRM), which increase with age and in response to amyloid proteins.

IRM cells respond to interferon proteins that the body releases to fight viral infections, such as SARS-CoV-2.

According to Dr. Rosa Sancho, head of research at Alzheimer’s Research UK, “Fairy early in the pandemic, people with dementia emerged as a group at particular risk of severe COVID-19.”

The current findings, published in the journal Brain, build on previous work by Dr. Salih.

The new study, led by Naciye Magusali, a doctoral candidate at UCL, focused on the genotyping of 2,547 human DNA samples. Of these, 1,313 were from people with a diagnosis of Alzheimer’s disease, and 1,234 were from controls without Alzheimer’s.

The authors identified a variant of the interferon-stimulated gene oligoadenylate synthetase 1 (OAS1) that can increase the risk of developing Alzheimer’s disease by an estimated 11–22{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}.

Scientists have also shown that OAS1, which regulates inflammatory proteins, contributes to the genetic risk associated with severe COVID-19 outcomes.

According to the current study, cells treated to mimic the effects of COVID-19 showed a lower expression of OAS1.

Dr. Salih explains: “The variant in OAS1 associated with disease is lowering OAS1 expression. This supports the idea that people with lower levels of OAS1 are more likely to show a chronic cytokine response or ‘cytokine storm.’”

The work shows that the body needs OAS1 to reduce the amount of inflammation-causing proteins. According to Dr. Salih:

“We see in […] microglial cells that OAS1 is suppressing pro-inflammatory function of cells in response to elevated levels of interferon.”

These findings show the importance of inflammation in both the progression of Alzheimer’s disease and the severity of COVID-19.

Speaking about the new research, Dr. Sancho points out that “[w]e don’t know whether the effects of this risk gene could influence long-term neurological consequences of COVID-19 or whether COVID-19 […] increases the risk of dementia later in life.”

Dr. David Strain, a senior clinical lecturer at the University of Exeter in the United Kingdom, comments: “It does add important information as to the pathogenesis of the more severe presentations of COVID-19 and will hopefully be able to shed further light on potential treatment options or even personalized preventive medicine.”

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