Non-Alzheimer Aβ deposits in the human CNS: Implications with hypoxia and related conditions

We recently reported the deposition of Aβ in the frontal cortex of individuals who died of acute coronavirus disease 2019 (COVID-19), or who did not have COVID-19 but had respiratory distress, or infants with severe cardiac malformations. These Aβ deposits were not the senile, neuritic core "plaques" of Alzheimer's disease (AD) and did not stain for Thioflavin-S or with antibodies to phosphorylated tau protein. Here, we examined multiple sections of the brains of such individuals, finding these non-Alzheimer Aβ deposits (NADAs) predominantly in the isocortex, including frontal, temporal, insular, and occipital, but also in subcortical structures such as the diencephalon, cerebellum, brainstem, and spinal cord, albeit many fewer. NADAs also appeared around blood vessels and within blood vessel walls, but did not incite an inflammatory response. We also examined brains of individuals with metabolic and mitochondrial diseases that lead to hypoxic damage and one individual with severe hyperthermia. All had NADAs identical to the ones we previously reported. These Aβ deposits somewhat resemble the amorphous or diffuse plaques or deposits that have been thought to be associated with early stages of AD, but they are morphologically distinguishable and appear in brains of young individuals who have no Alzheimer pathology. We suggest that the deposits are associated with hypoxia or related mechanisms of injury.