COVID-19 amplifies damage to the central nervous system in Alzheimer's disease Alzheimers Disease CentralNervousSystem CNS Coronavirus COVID Encephalitis Endothelialitis SpikeProtein Microvasculature ElsevierNews GnomeDx OhioState RutgersU
Studies have reported that the human brain is highly susceptible to severe acute respiratory syndrome coronavirus 2 -associated pathological changes. In addition, pre-existing AD has been established to increase the risk of fatal COVID-19, and conversely, COVID-19 has been linked to enhanced unmasked AD incidence rates. However, the molecular mechanisms of AD amplification by SARS-CoV-2 have not been understood completely.
The study participants were aged between 50 years and 92 years, and most of them were men. Samples were obtained from the frontal cortex, hippocampus, or brainstem/midbrain regions of the brain and subjected to immunohistochemistry analysis to determine titers of antibodies against the SARS-CoV-2 spike protein subunits 1 and 2 , nucleocapsid protein, furin, angiotensin-converting enzyme and hyperphosphorylated tau protein.
Results IHC analyses for β-amyloid-42, T protein, and α-synuclein confirmed AD and LBD diagnoses among SARS-CoV-2-positive individuals. In addition, brain samples of individuals with COVID-19-associated deaths without dementia history exhibited diffuse microangiopathy and S1 protein and S2 protein endocytosis by CD31+ endothelial cells with strong caspase-3, ACE2, IL-6, complement component 6 and TNF-α co-localization unrelated to SARS-CoV2 RNA levels.
Microencephalitis in SARS-CoV-2-infected tissues was MAP-based and marked by degeneration of endothelial cells, microthrombi, and perivascular edema with immunological responses seated primarily in the reactive endogenous microglia. Microthrombi were observed in the SARS-CoV-2-infected tissues only, with density equivalent for SARS-CoV-2-positive non-dementia cases and COVID-19/AD individuals of 5.3+ microvessels per cm2 [standard electron microscopy 1.5].