IN COGNITIVELY NORMAL INDIVIDUALS, THE BEST CONCORDANCE BETWEEN CSF BIOMARKERS AND PET AMYLOID IS OBSERVED WITH THE COMBINATION OF B-AMYLOID1-42 AND PHOSPHORYLATED TAU

Abstract

The concept of emerging preclinical stage of Alzheimer disease (AD) is based on the presence of AD pathological markers in cognitively normal individuals. Since brain amyloidosis can be evidenced by amyloid PET or CSF biomarkers, it is of importance to determine the concordance between these two approaches. In a population of cognitively normal individuals, we compared the concordance of different CSF biomarkers with 18-Florbetapir uptake and examined their accuracy to predict PET amyloid status. The study population was a part of the monocentric prospective longitudinal Insight-preAD cohort, including cognitively normal individuals, with defined brain 18 F-Florbetapir-PET amyloid status, and optional CSF investigations. CSF Total tau (Tau), phosphorylated Tau (P-tau) and b-amyloid peptides, (Ab40) and (Ab42), were measured using Innotest-Elisa kits (Fujirebio). Among participants, 26 men and 25 women underwent both PET amyloid imaging and CSF sampling at inclusion. Eleven subjects (21.5%) were classified as PET positive (PET+) and 40 (78.4%) as PET negative (PET-). There was no significant difference in age between PET+ (76.4 + 3.6 y) and PET- (75.9 + 3.4 y) subjects. CSF biomarkers and their ratio discriminate between PET- and PET+ subjects with accuracy ranging from AUC=0.82 for Tau to AUC=0.995 for P-Tau/Ab42 ratio. The highest accuracy to predict PET positivity was observed for P-tau/Ab42 ratio, with 100% sensitivity and 97.5% specificity. At the optimal cutoffs, the number false positive (PET - individuals with abnormal CSF marker), were 5 (9.8%), 4 (8%), 3 (6%) and 1 (2%) when using Ab42, Ab40/Ab42, Tau/Ab42 and P-tau/Ab42, respectively. The number of false positive (PET+ individuals with normal CSF values) was 2 (4%) and 1 (2%), when using Ab42 and Ab40/Ab42, respectively and no false negative subjects were found, with Tau/Ab42 and P-tau/Ab42 ratio. In cognitively normal individuals, CSF P-tau/Ab42 and Tau/Ab42 showed a better concordance with amyloid PET than Ab42 or Ab40/Ab42. This finding suggests that at preclinical AD stage, amyloid PET should not be considered in the binary positive or negative fashion as higher SUVr subjects also display increased tau and P-tau in the CSF suggesting imminent clinical expression of the disease.