Antemortem CSF Aβ42/Aβ40 ratio predicts Alzheimer's disease pathology better than Aβ42 in rapidly progressive dementias

Objective: Despite the critical importance of pathologically confirmed samples for biomarker validation, only a few studies have correlated CSF Aβ42 values invivo with postmortem Alzheimer's disease (AD) pathology, while none evaluated the CSF Aβ42/Aβ40 ratio. We compared CSF Aβ42 and Aβ42/Aβ40 ratio as biomarkers predicting AD neuropathological changes in patients with a short interval between lumbar puncture and death. Methods: We measured CSF Aβ40 and Aβ42 and assessed AD pathology in 211 subjects with rapidly progressive dementia (RPD) and a definite postmortem diagnosis of Creutzfeldt-Jakob disease (n=159), AD (n=12), dementia with Lewy bodies (DLB, n=4), AD/DLB mixed pathologies (n=5), and various other pathologies (n=31). Results: The score reflecting the severity of Aβ pathology showed a better correlation with ln(Aβ42/Aβ40) (R 2 =0.506, β=−0.713, P&nbsp