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

Acta Neuropathol. 2024 May 27;147(1):92. doi: 10.1007/s00401-024-02743-9.

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: Alzheimer’s disease; Brain; COVID-19; Corona viruses; Down syndrome; Glial cells; Neurologic symptoms; SARS-CoV-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / virology
  • Amyloid beta-Peptides / metabolism
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Astrocytes / virology
  • Brain* / pathology
  • Brain* / virology
  • COVID-19* / complications
  • COVID-19* / pathology
  • Down Syndrome* / complications
  • Down Syndrome* / metabolism
  • Down Syndrome* / pathology
  • Female
  • Humans
  • Male
  • Microglia / metabolism
  • Microglia / pathology
  • Middle Aged
  • SARS-CoV-2 / pathogenicity
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins