The Senescent Front: The Cell Biology of Alzheimer's Timeline

This dissertation proposes that cellular senescence provides the specific biological mechanism for the age-dependent progression of Alzheimer's. It maps the transition of brain cells into a senescent state — where cells stop functioning and secrete inflammatory signals (the SASP) — across three chronological phases: neuronal ignition in the brainstem, microglial collapse in the hippocampus, and systemic disintegration of protective networks. With the SASP draining NAD+ as the "engine" of aging, senolytic therapies must be precisely timed to the cell types failing in each decade. Alzheimer's becomes a sequential failure of cell biology over time. Read the paper: https://www.adultcognitivedisease.com