This hypothesis proposes that In Alzheimer's disease, biomarker events occur in a specific temporal sequence: amyloid-β abnormalities (CSF and PET) first, followed by tau abnormalities (CSF), then structural brain volume changes (hippocampus, entorhinal), followed by cognitive changes, then widespread brain volume changes, with the full progression taking approximately 17.3 years.
Type: Causal Chain
Confidence: Supported
Related Diseases: Alzheimer's disease
TEBM analysis of ADNI dataset revealed: Aβ abnormality at 0 years, tau abnormalities at 2.65-2.7 years, hippocampus at 5.1 years, entorhinal at 5.7 years, cognitive changes at 7.5 years, mid-temporal at 10.4 years. Validated in OASIS dataset with 95% CI agreement.
Amyloid-β, tau, CSF biomarkers, hippocampus, entorhinal, ADAS13, MMSE, RAVLT, sMRI, PET
This hypothesis is supported by multiple lines of evidence from the literature.