Publications in Alzheimer’s & Dementia: The Journal of the Alzheimer's Association
The mission of Alzheimer's & Dementia: Journal of the Alzheimer's Association is to bridge the knowledge gaps across a wide range of bench-to-bedside investigation. The journal publishes the results of studies in: behavior, biochemistry, genetics, molecular biology, pharmacology, physiology, protein chemistry, neurology, neuropathology, psychiatry, geriatrics, neuropsychology, epidemiology, sociology, health services research, health economics, political science and public policy. Content emphasizes interdisciplinary investigations, integrative/translational articles, related to: etiology, risk factors, early detection, disease modifying interventions, prevention of dementia and applications of new technologies in health services.
Alzheimer’s disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain
INTRODUCTION: While there may be microbial contributions to Alzheimer’s disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+)microglia subtype associated with increased immunoglobulinG4(IgG4) in the transverse colon (TC).
METHODS: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.
RESULTS: CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death.
DISCUSSION: Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+)microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+)microglia.
Research Fields
Biology, Genetics & Heredity, Neurology & Neurosurgery
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