Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2: preliminary findings.

Document Type

Article

Abstract

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

Keywords

Humans, Down Syndrome, Alzheimer Disease, COVID-19, Male, Female, Aged, Middle Aged, Brain, Aged, 80 and over, Astrocytes, Amyloid beta-Peptides, SARS-CoV-2, Microglia, Adult, tau Proteins

Medical Subject Headings

Humans; Down Syndrome; Alzheimer Disease; COVID-19; Male; Female; Aged; Middle Aged; Brain; Aged, 80 and over; Astrocytes; Amyloid beta-Peptides; SARS-CoV-2; Microglia; Adult; tau Proteins

Publication Date

5-27-2024

Publication Title

Acta Neuropathol

ISSN

1432-0533

Volume

147

Issue

1

First Page

92

Last Page

92

PubMed ID

38801558

Digital Object Identifier (DOI)

10.1007/s00401-024-02743-9

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