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Background: Alzheimer's disease (AD)-related tauopathy can be measured with CSF phosphorylated tau (pTau) and tau PET. We aim to investigate the associations between these measurements and their relative ability to predict subsequent disease progression. Methods: In 219 cognitively unimpaired and 122 impaired Alzheimer's Disease Neuroimaging Initiative participants with concurrent amyloid-β (Aβ) PET (18 F-florbetapir or 18 F-florbetaben), 18 F-flortaucipir (FTP) PET, CSF measurements, structural MRI, and cognition, we examined interrelationships between these biomarkers and their predictions of subsequent FTP and cognition changes. Results: The use of a CSF pTau/Aβ 40 ratio eliminated positive associations we observed between CSF pTau alone and CSF Aβ 42 in the normal Aβ range likely reflecting individual differences in CSF production rather than pathology. Use of the CSF pTau/Aβ 40 ratio also increased expected associations with Aβ PET, FTP PET, hippocampal volume, and cognitive decline compared to pTau alone. In Aβ+ individuals, abnormal CSF pTau/Aβ 40 only individuals (26.7%) were 4 times more prevalent (p < 0.001) than abnormal FTP only individuals (6.8%). Furthermore, among individuals on the AD pathway, CSF pTau/Aβ 40 mediates the association between Aβ PET and FTP PET accumulation, but FTP PET is more closely linked to subsequent cognitive decline than CSF pTau/Aβ 40. Conclusions: Together, these findings suggest that CSF pTau/Aβ 40 may be a superior measure of tauopathy compared to CSF pTau alone, and CSF pTau/Aβ 40 enables detection of tau accumulation at an earlier stage than FTP among Aβ+ individuals.

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Introduction Positron emission tomography targeting tau (tau‐PET) is a promising diagnostic tool for the identification of Alzheimer's disease (AD). Currently available data rely on quantitative measures, and a visual interpretation method, critical for clinical translation, is needed. Methods We developed a visual interpretation method for 18F‐flortaucipir tau‐PET and tested it on 274 individuals (cognitively normal controls, patients with mild cognitive impairment [MCI], AD dementia, and non‐AD diagnoses). Two readers interpreted 18F‐flortaucipir PET using two complementary indices: a global visual score and a visual distribution pattern. Results Global visual scores were reliable, correlated with global cortical 18F‐flortaucipir standardized uptake value ratio (SUVR) and were associated with clinical diagnosis and amyloid status. The AD‐like 18F‐flortaucipir pattern had good sensitivity and specificity to identify amyloid‐positive patients with AD dementia or MCI. Discussion This 18F‐flortaucipir visual rating scheme is associated with SUVR quantification, clinical diagnosis, and amyloid status, and constitutes a promising approach to tau measurement in clinical settings.

Little is known about the association between personality and Alzheimer's disease (AD) biomarkers, and existing results are inconsistent. We aimed to determine whether personality was associated with ␤-amyloid (A␤) accumulation in cognitively normal aging. One hundred twenty-nine participants were included in this cross-sectional study. Personality was measured with the Big Five Inventory (BFI) and brain A␤ deposition was assessed with [ 11 C] Pittsburgh compound B (PiB)-positron emission tomography (PET) imaging. Conscientiousness scores had a negative association with global PiB distribution volume ratio (DVR) in all participants after adjusting for age, sex, education, and vascular risk factors (␤[SE] ϭ Ϫ0.19[0.09], 95% confidence interval [CI: Ϫ0.35, Ϫ0.02], p ϭ .031), while agreeableness, extraversion, neuroticism, and openness had no association with global PiB DVR. Assuming the relative stability of personality traits, these findings suggest that conscientiousness may protect against A␤ accumulation in cognitively normal aging through mechanisms that are as yet unknown.