1. Neuropathological findings in Down syndrome, Alzheimer’s disease and control patients with and without SARS-COV-2: preliminary findings
- Author
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Granholm, Ann-Charlotte E, Englund, Elisabet, Gilmore, Anah, Head, Elizabeth, Yong, William H, Perez, Sylvia E, Guzman, Samuel J, Hamlett, Eric D, and Mufson, Elliott J
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Neurodegenerative ,Acquired Cognitive Impairment ,Intellectual and Developmental Disabilities (IDD) ,Brain Disorders ,Aging ,Alzheimer's Disease ,Coronaviruses Disparities and At-Risk Populations ,Infectious Diseases ,Dementia ,Emerging Infectious Diseases ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Coronaviruses ,Down Syndrome ,2.1 Biological and endogenous factors ,Neurological ,Good Health and Well Being ,Humans ,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 ,Corona viruses ,Neurologic symptoms ,Alzheimer's disease ,Glial cells ,Down syndrome ,Alzheimer’s disease ,Clinical Sciences ,Neurology & Neurosurgery - 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.
- Published
- 2024