Clinical utility of plasma biomarkers to identify preclinical Alzheimer’s disease in the community

Abstract

AbstractBackgroundSeveral plasma biomarkers have shown good correlation with brain amyloidosis measured by CSF biomarkers and PET, but their utility to identify subjects with Alzheimer’s disease(AD) brain pathology at the community level is not well known. Neuropsychological tests might be a more accessible alternative.MethodOur aims were to assess the utility of plasma p‐tau231, plasma GFAP, and plasma NFL to identify individuals with preclinical AD, and to compare it with the utility of current neuropsychological tests for early AD detection: Preclinical Alzheimer's Cognitive Composite 5(PACC5), Spanish version of Face‐Name Memory Exam(S‐FNAME), Logical Memory Test (LMT‐WMSIII), and Free and Cued Selective Reminding Test(FCSRT). Our study population was a community‐based cohort that enrolls individuals older than 55 living in Cantabria, a region in northern Spain. Exclusion criteria include a diagnosis of dementia or other cognitive disorders. AD+ status was defined by abnormal levels of both CSF amyloid‐β1‐42/1‐40 ratio and CSF p‐tau181. General linear models were used to compare biomarker and cognitive results between AD+ subjects and the rest of the population, with age and sex as covariates. ROC curves were built to compare the utility of each test to identify AD+ cases.ResultThe total sample included 156 individuals, 30 of them AD+. AD+ subjects showed significantly higher levels of GFAP (mean difference 78.04, p<0.00001) and p‐tau231 (mean difference 5.53, p 0.00040), but not NFL (mean difference 1.16, p 0.63), compared to non‐AD (table 1). After adjusting by age, sex, APOE4 carrier status, and AD status, age and sex were still independent predictors of GFAP levels, but not of p‐tau231 (table 2). FCSRT delayed recall and LMT‐WMSIII total score were significantly lower in AD+ than in non‐AD cases, but not S‐FNAME nor PACC5 (table 1). Both plasma GFAP and p‐tau231 showed an AUC of 0.75 to identify AD+ individuals (table 3, figure 1). Neuropsychological tests obtained non‐significantly smaller AUC than plasma biomarkers.ConclusionIn our community‐based population, plasma GFAP and p‐tau231 were useful to identify individuals with preclinical AD, but not plasma NFL. Although probably with a lower performance, early detection cognitive tests may also be helpful to identify AD cases in the community.