Aß Deposits in the Neocortex of Adult and Infant Hypoxic Brains, Including in Cases of COVID-19.

The brain of a 58-year-old woman was included as a civilian control in an ongoing autopsy study of military traumatic brain injury (TBI). The woman died due to a polysubstance drug overdose, with Coronavirus Disease 2019 (COVID-19) serving as a contributing factor. Immunohistochemical stains for ß-amyloid (Aß), routinely performed for the TBI study, revealed numerous, unusual neocortical Aß deposits. We investigated the autopsied brains of 10 additional young patients (<60 years old) who died of COVID-19, and found similar Aß deposits in all, using two different Aß antibodies across three different medical centers. The deposits failed to stain with Thioflavin-S. To investigate whether or not these deposits formed uniquely to COVID-19, we applied Aß immunostains to the autopsied brains of COVID-19-negative adults who died with acute respiratory distress syndrome and infants with severe cardiac anomalies, and also biopsy samples from patients with subacute cerebral infarcts. Cortical Aß deposits were also found in these cases, suggesting a link to hypoxia. The fate of these deposits and their effects on function are unknown, but it is possible that they contribute to the neurocognitive sequelae observed in some COVID-19 patients. Our findings may also have broader implications concerning hypoxia and its role in Aß deposition in the brain.

Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature.

BACKGROUND: The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models. METHODS: Studies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias. FINDINGS: Of 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters. INTERPRETATION: Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.