Abstract
AbstractBackgroundThe biological definition of Alzheimer’s disease (AD) based on cerebrospinal fluid (CSF) biomarkers requires both abnormal amyloid (A) and p‐tau (T). However, previous studies showed that up to 32% of individuals with autopsy‐confirmed AD show normal p‐tau levels in CSF in vivo. We studied in two independent cohorts how often individuals with abnormal CSF amyloid and normal p‐tau levels had autopsy‐confirmed AD, and whether these individuals differed in pathological amyloid and tau scores compared to individuals with both abnormal CSF amyloid and p‐tau levels.MethodIn total we included 118 individuals with CSF collection and autopsy from the Amsterdam Dementia Cohort (ADC) (n=75, mean±SD age 62±9 years, 26 (35%) female, 37 (49%) with AD at autopsy) and from ADNI (n=43, mean±SD age 77±7 years, 9 (21%) female, 31 (72%) with AD at autopsy). The mean time between CSF collection and death was 4.5±2.9 years in ADC and 5.1±2.5 years in ADNI. Biomarker profiles were based on dichotomized CSF Aβ42 and p‐tau (ApT) (ADC: Innotest ELISA, ADNI: Elecsys). We assessed the diagnostic accuracy of ApT profiles to detect autopsy‐confirmed AD, and investigated differences in degree of AD neuropathology (based on A‐score for Thal stage, B‐score for Braak stage and C‐score for CERAD score; available in n=36 (48%) ADC individuals and all ADNI individuals) between A+pT+ and A+pT‐ individuals with and without autopsy‐confirmed AD.ResultAll individuals with an A+pT+ profile had AD at autopsy (27/27 in ADC, 23/23 in ADNI). Of individuals with an A+pT‐ profile 7/13 (54%) individuals in ADC and 5/8 A+pT‐ (64%) in ADNI had AD at autopsy. In both cohorts, CSF amyloid status showed the highest accuracy to detect autopsy‐confirmed AD (86‐88%) and the addition of CSF p‐tau status did not improve this (81%‐87%). Comparing individuals on A, B and C neuropathological scores, we observed no differences in degree of AD neuropathology between A+pT‐ and A+pT+ individuals with autopsy‐confirmed AD. A+pT‐ individuals without AD at autopsy had low neuropathological scores.ConclusionOur results indicate that a normal p‐tau concentration in the presence of an abnormal amyloid marker does not exclude the presence of AD at autopsy.
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