Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease.

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is diagnosed via postmortem detection of extracellular amyloid beta (Aβ) plaques or oligomers and intracellular hyperphosphorylated tau. These canonical pathologies are key players in AD etiology. A complementary line of research suggests that common human pathogens serve as the initial seeding agents which facilitate the pathologies of AD.

Altered Gut Microbial Load and Immune Activation in a Model of Human Tauopathy.

Tau is a microtubule-associated protein that stabilizes the neuronal cytoskeleton. In the family of neurodegenerative diseases known as tauopathies, including Alzheimer's disease (AD), frontotemporal dementia (FTD), and chronic traumatic encephalopathy (CTE), abnormal tau aggregation destabilizes microtubule structure, contributing to a cascade of cellular processes leading to neuronal cell death. The gut microbiome has increasingly become a target of neurodegenerative disease research since gut microbiome imbalances have been linked to protein aggregation and inflammation through a bidirectional axis linking the gut and brain.