Astrocytic Calcium and Default Mode Network Dysfunction in Early Stage AD
Alzheimer's Disease - Diagnostics, Pathogenesis, and Treatment [Working Title] July 1, 2026 Denis Larrivee
Evidence suggests that nonneuronal cells, particularly astrocytes, may be a primary site of pathogenesis in early Alzheimer's disease. Functional connectivity changes in the cingulate cortex, a hub of the default mode network, appear years before amyloid plaques and neurofibrillary tangles. Dysfunctional calcium signaling occurs in astrocytes but not neurons, paralleling these connectivity changes; restoring normal calcium reverses them. Astrocytes support bidirectional communication with neurons and coordinate network activity. Studying calcium signaling in default mode network astrocytes could yield insights into early Alzheimer's pathogenesis, integrating findings on connectivity disruption and calcium dysfunction to assess astrocyte influence.