Alzheimer's Imaging Consortium.

Background: Amyloid-negative tau-positive PET (A-T+) participants have been reported in several studies. We assessed the prevalence and characteristics of A-T+ participants in a cohort of cognitively unimpaired individuals with a first-degree family history of Alzheimer's disease (AD) dementia.

Method: We studied 252 participants from the longitudinal PREVENT-AD cohort (mean cognitive follow-up = 3.42 years, SD = 2.86) who received an amyloid (18F-NAV4694) and a tau (18F-Flortaucipir) PET-scan. The amyloid-positivity threshold was 18 centiloids (SUVR=1.27) and tau positive threshold was set as 2SD above the mean of A- participants in a temporal meta-ROI (SUVR=1.29). Follow-up PET scans were available for 109 participants. We characterized A-T+ participants on clinical (age, sex, APOE4 status, education, depression, apathy, anxiety, sleep), cognitive (RBANS, MMSE, ECoG) and fluid (CSF, plasma) measurements.

Result: In the PREVENT-AD cohort, only 3 (1.2 %) of all studied participants were classified as A-T+ (see Table 1 for participants characteristics). Participants 1 and 2 were positive based on plasma Aß42/40 and they had relatively low levels of tau binding that could represent early pathology. Participant 3 was also positive based on CSF and plasma, her Aß-PET scan was classified as positive on visual read and became quantitatively positive at follow-up. Participant 3 had extensive unilateral tau binding at baseline that became bilateral at follow-up (Figure 1). Figure 2 details the longitudinal cognitive trajectory of Participant 3. During the cognitive follow-up, participants 1 developed mild cognitive impairment and participant 3 developed dementia.

Conclusion: A-T+ individuals are rare in the PREVENT-AD cohort and the 3 A-T+ were classified as Aß positive based on fluid biomarkers. One of the 3 A-T+ individuals showed a very fast clinical progression and a tau uptake pattern atypical of AD.