The cerebrospinal fluid “Alzheimer profile”: Easily said, but what does it mean?

TLDR: In this paper, the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-s 1-42 (Aβ 42 ), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD) was identified.

Abstract: Background We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-s 1-42 (Aβ 42 ), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD). Methods We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). Results Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/Aβ 42 ratio and 0.08 for the p-tau/Aβ 42 ratio. Ratios performed similar to formulas (sensitivity, 91%–93%; specificity, 81%–84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/Aβ 42 ratio. Conclusions A tau/Aβ 42 ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.