Recapitulation of pathophysiological features of AD [Alzheimer’s disease] in SARS-CoV-2 infected subjects, 2022/3, Griggs et al

Preprint
See post 5 for published version

Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals
Elizabeth Griggs, Kyle Trageser, Sean Naughton, Eun-Jeong Yang, Brian Mathew, Grace Van Hyfte, Linh Hellmers, Nathalie Jette, Molly Estill, Li Shen, Tracy Fischer, Giulio Maria Pasinetti

Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimers disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases.

Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.

BioRxiv

 

This appears to be an in-depth examination.

A question arises, especially as I note the researchers found "similar alterations of neuroinflammation and blood-brain barrier integrity" in the groups studied: why is this not studied more for pwME?

It seems ridiculous that more studies of this ilk are not being done for pwME.

I know it's extremely difficult to get research funding for ME, but the stinginess is just beyond the pale.

There was this 2014 study that found neuroinflammation; we need this replicated:https://pubmed.ncbi.nlm.nih.gov/24665088/

"2014 Jun;55(6):945-50.
doi: 10.2967/jnumed.113.131045. Epub 2014 Mar 24.
Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An ¹¹C-(R)-PK11195 PET Study
Yasuhito Nakatomi 1, Kei Mizuno 2, Akira Ishii 3, Yasuhiro Wada 3, Masaaki Tanaka 3, Shusaku Tazawa 3, Kayo Onoe 4, Sanae Fukuda 3, Joji Kawabe 5, Kazuhiro Takahashi 3, Yosky Kataoka 3, Susumu Shiomi 5, Kouzi Yamaguti 6, Masaaki Inaba 7, Hirohiko Kuratsune 8, Yasuyoshi Watanabe 9
Affiliations

• PMID: 24665088
  
• DOI: 10.2967/jnumed.113.131045

Free article
Abstract


Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation. (11)C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide ((11)C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used (11)C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients.

Methods: Nine CFS/ME patients and 10 healthy controls underwent (11)C-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, nondisplaceable binding potential (BP(ND)) values were determined using linear graphical analysis with the cerebellum as a reference region.

Results: The BP(ND) values of (11)C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BP(ND) values of (11)C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BP(ND) values in the cingulate cortex and thalamus positively correlated with pain score, and the BP(ND) value in the hippocampus positively correlated with depression score.

Conclusion: Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

Keywords: 11C-(R)-PK11195; chronic fatigue syndrome (CFS); myalgic encephalomyelitis (ME); neuroinflammation; positron emission tomography (PET).

© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc."

 

There is a brain bank in the UK and with the NIH in the USA, there just isn't any researchers interested in bodies/brains from ME/CFS patients and presumably not in Long Covid either.

 

Published as —

Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects
Elizabeth Griggs; Kyle Trageser; Sean Naughton; Eun-Jeong Yang; Brian Mathew; Grace Van Hyfte; Linh Hellmers; Nathalie Jette; Molly Estill; Li Shen; Tracy Fischer; Giulio Maria Pasinetti

Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition in some patients with post-acute sequelae of SARS-CoV-2 (PASC). To evaluate neuropathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Brodmann area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer’s disease (AD), and SARS-CoV-2-infected AD individuals compared to age-and gender-matched neurological cases.

Here, we show similar alterations of neuroinflammation and blood–brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2-infected AD individuals. Distribution of microglial changes reflected by the increase in Iba-1 reveals nodular morphological alterations in SARS-CoV-2-infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status.

The finding may help in informing decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.

Editor's evaluation

This study compares neuropathological changes in postmortem brain samples from patients with SARS-CoV-2 infection, Alzheimer's disease, both SARS-CoV-2 and Alzheimer's disease, and demographically matched controls. This is an important comparison that expands information on SARSCoV-2 effects in the brain. Solid results are presented to support the main claims.

Link | Paywall (eLife)