Amyloid PETs are commonly negative in suspected Alzheimer's disease with an increase in CSF phosphorylated-tau protein concentration but an A42 concentration in the very high range: a prospective study

BackgroundAtypical cerebrospinal fluid (CSF) patterns, involving an increase in the concentration of phosphorylated-tau (P-tau) proteins but normal amyloid- concentration, are not uncommon in patients with mild neurocognitive disorders and suspected Alzheimer's disease (AD). In these conditions, however, AD diagnosis may be ruled out in the absence of any amyloid deposition at positron-emission tomography (PET). This pilot cross-sectional study was aimed to determine whether this negativity of amyloid PET can be predicted by CSF profiles in such patients.MethodsTwenty-five patients (73 [68-80]years, 10 women) with mild neurocognitive disorders, suspected AD and an increase in the CSF concentration of P-tau proteins but normal A42 concentration and A42/A40 ratio were prospectively included and referred to a F-18-florbetaben PET. The latter was considered as definitively negative with the conjunction of both visual (brain amyloid plaque load score) and quantified (standard uptake value ratios) criteria. Predictors of a negative PET were searched among current CSF biomarkers (A ss 42, A ss 40, T-tau, P-tau, A ss 42/A ss 40, A ss 42/p-tau).ResultsAmyloid PET was negative in 15 patients (60%) with a CSF A ss 42 concentration being the sole independent predictor of this negativity. The criterion of an A ss 42 concentration in the very high range (>843pg/mL), observed in 60% (15/25) of the study patients, was associated with a negative amyloid PET in 93% (14/15) of cases.ConclusionsIn mild neurocognitive disorders patients with suspected AD and showing an increase in CSF P-tau protein level, amyloid PETs are commonly negative, when A ss 42 concentration is in the very high range. In such case, AD diagnosis based on biomarkers can be ruled out with reasonable certainty, without the need for additional CSF second-line assays or results from amyloid PET.