Antemortem CSF A?42/A?40 ratio predicts Alzheimer's disease pathology better than A?42 in rapidly progressive dementias.

ABSTRACT:

Objective

Despite the critical importance of pathologically confirmed samples for biomarker validation, only a few studies have correlated CSF A?42 values in vivo with postmortem Alzheimer's disease (AD) pathology, while none evaluated the CSF A?42/A?40 ratio. We compared CSF A?42 and A?42/A?40 ratio as biomarkers predicting AD neuropathological changes in patients with a short interval between lumbar puncture and death.

Methods

We measured CSF A?40 and A?42 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 A? pathology showed a better correlation with ln(A?42/A?40) (R ² = 0.506, ? = -0.713, P < 0.001) than with ln(A?42) (R ² = 0.206, ? = -0.458, P < 0.001), which was confirmed after adjusting for covariates. A?42/A?40 ratio showed significantly higher accuracy than A?42 in the distinction between cases with or without AD pathology (AUC 0.818 ± 0.028 vs. 0.643 ± 0.039), especially in patients with A?42 levels ?495 pg/mL (AUC 0.888 ± 0.032 vs. 0.518 ± 0.064). Using a cut-off value of 0.810, the analysis of A?42/A?40 ratio yielded 87.0% sensitivity, 88.2% specificity in the distinction between cases with an intermediate-high level of AD pathology and those with low level or no AD pathology.

Interpretation

The present data support the use of CSF A?42/A?40 ratio as a biomarker of AD pathophysiology and noninvasive screener for A? pathology burden, and its introduction in the research diagnostic criteria for AD.

SUBMITTER: Baiardi S 

PROVIDER: S-EPMC6389744 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature