Individuals with Alzheimer's disease and low tau burden: Characteristics and implications.

ABSTRACT

INTRODUCTION: Abnormal amyloid-beta (Aß) and tau deposition define Alzheimer's Disease (AD), but non-elevated tau is relatively frequent in patients on the AD pathway. METHODS: We examined characteristics and regional patterns of 397 Aß+ unimpaired and impaired individuals with low tau (A+T-) in relation to their higher tau counterparts (A+T+). RESULTS: Seventy-one percent of Aß+ unimpaired and 42% of impaired Aß+ individuals were categorized as A+T- based on global tau. In impaired individuals only, A+T- status was associated with older age, male sex, and greater cardiovascular risk. α-synuclein was linked to poorer cognition, particularly when tau was low. Tau burden was most frequently elevated in a common set of temporal regions regardless of T+/T- status. DISCUSSION: Low tau is relatively common in patients on the AD pathway and is linked to comorbidities that contribute to impairment. These findings have implications for the selection of individuals for Aß- and tau-modifying therapies.