Small study finds Alzheimer's-like changes in some COVID patients'
brains

Date:
February 3, 2022
Source:
Columbia University Irving Medical Center
Summary:
A study reports that the brains of a small sample of patients who
died of COVID display some of the same molecular changes found in
the brains of people with Alzheimer's disease.



FULL STORY ==========================================================================
A study from researchers at Columbia University Vagelos College of
Physicians and Surgeons reports that the brains of a small sample of
patients who died of COVID display some of the same molecular changes
found in the brains of people with Alzheimer's disease.


==========================================================================
The findings could help explain the memory problems reported by sufferers
of "long COVID," though the researchers caution that the study is small --
with data from only 10 patients -- and needs to be replicated by others.

The study was published Feb. 3 in Alzheimer's & Dementia: The Journal
of the Alzheimer's Association.

Early reports of "brain fog" and persistent cardiac symptoms in COVID
survivors prompted the Columbia researchers to investigate how certain molecules called ryanodine receptors were affected in this new disease.

Defective ryanodine receptors have been implicated in diverse pathogenic processes, ranging from heart and lung disease to the brain's response
to stress and Alzheimer's disease, as reported in research led by Andrew
Marks, MD, chair of the Department of Physiology & Cellular Biophysics
at the Vagelos College of Physicians and Surgeons, who led the new study.

"When the COVID pandemic hit, like everybody else I was interested in
being helpful and doing what we could do," says Marks. "What we found
is really I think quite unexpected: Not only did we find defective
ryanodine receptors in the hearts and lungs of deceased COVID patients,
we also found them in their brains." Molecular changes


========================================================================== Inside neurons, defective ryanodine receptors have previously been
linked to an increase in phosphorylated tau, a well-known hallmark
of Alzheimer's.

In the new study, the Columbia researchers found high levels of
phosphorylated tau in the brains of the COVID patients in addition to
defective ryanodine receptors.

Phosphorylated tau was found in areas where tau is typically located
in Alzheimer's patients, as well as in areas where tau is not typically
located in Alzheimer's patients. That suggests that phosphorylated tau
in the COVID patients could be a sign of early-stage Alzheimer's and also contribute to other neurological symptoms observed in COVID-19 patients.

Increased levels of phosphorylated tau in the brain are believed to be
linked to memory problems in Alzheimer's and could be causing similar
issues in people with long COVID, Marks says.

Based on the findings, together with additional changes found in the
brain, the investigators theorize that the immune response characteristic
of severe COVID causes inflammation in the brain, which in turn leads to dysfunctional ryanodine receptors and then increases in phosphorylated
tau. No changes in the pathways that lead to the formation of amyloid
beta -- another hallmark of Alzheimer's -- were found.



========================================================================== Future directions "One interpretation of these findings is that long
COVID could be an atypical form of Alzheimer's and/or that patients who
had severe COVID could be predisposed to developing Alzheimer's later in
life," says Marks, "but much more research needs to be done before we
can make more definitive conclusions." If the memory and neurological
problems of long COVID can be traced to defective ryanodine receptors,
a drug under development by Marks may help. The drug is now in early
clinical trials to treat a muscle disease caused by an inherited defect
in the ryanodine receptor. The drug was able to fix the ryanodine defect
when applied to the COVID patients' brain tissue.

"My greatest hope is that other laboratories will look into our findings,
and if they are validated, generate interest in a clinical trial for
long COVID," says Marks.

More information The research appears in a paper titled, "Alzheimer's-like signaling in brains of COVID-19 patients." Andrew Marks is professor
and chair of the Department of Physiology & Cellular Biophysics and the Clyde'56 and Helen Wu Professor of Molecular Cardiology (in Medicine)
at the Vagelos College of Physicians and Surgeons and professor of
biomedical engineering at Columbia University's Fu Foundation School of Engineering and Applied Science.

All authors: Steve Reiken, Leah Sittenfeld, Haikel Dridi, Xiaoping Liu,
and Andrew R. Marks (all from Columbia).

The research was supported by the NIH (grant R01NS114570).

Columbia University and Andrew Marks own stock in ARMGO Pharma Inc.,
a company developing compounds targeting the ryanodine receptor, and
have patents on the compounds. Steven Reiken has consulted for ARMGO
Pharma in the past 36 months.

special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by
Columbia_University_Irving_Medical_Center. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Steve Reiken, Leah Sittenfeld, Haikel Dridi, Yang Liu, Xiaoping Liu,
Andrew R. Marks. Alzheimer's‐like signaling in brains
of COVID‐19 patients. Alzheimer's & Dementia, 2022; DOI:
10.1002/ alz.12558 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220203122947.htm

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