UC San Diego

Recently proposed biomarker-only diagnostic frameworks propose that amyloid-beta is necessary for placement on the Alzheimers disease continuum, whereas tau in the absence of amyloid-beta is considered to be a non-Alzheimers disease pathologic change. Similarly, the pathologic designation of tau in the absence of amyloid-beta is characterized as primary age-related tauopathy and separable from Alzheimers disease. Our study sought to identify an early-to-moderate tau stage with minimal amyloid-beta using PET imaging and characterize these individuals in terms of clinical, cognitive and biological features. Seven hundred and three participants from the Alzheimers Disease Neuroimaging Initiative were classified into one of the four groups (A-/T-, A-/T+, A+/T- and A+/T+) based on PET positivity or negativity for cortical amyloid-beta (A-/A+) and early-to-moderate stage (i.e. meta-temporal) tau (T-/T+). These groups were then compared on demographic and clinical features, vascular risk, multi-domain neuropsychological performance, multi-domain subjective cognitive complaints, apolipoprotein E epsilon-4 carrier status and cortical thickness across Alzheimers disease-vulnerable regions. The proportion of participants classified in each group was as follows: 47.23% A-/T-, 13.51% A-/T+, 12.23% A+/T- and 27.03% A+/T+. Results indicated that the A-/T+ and A+/T+ groups did not statistically differ on age, sex, depression levels, vascular risk and cortical thickness across temporal and parietal regions. Additionally, both A-/T+ and A+/T+ groups showed significant associations between memory performance and cortical thickness of temporal regions. Despite the different pathologic terminology used for A-/T+ and A+/T+, these groups did not statistically differ on a number of clinical, cognitive and biomarker features. Although it remains unclear whether A-/T+ reflects a pathologic construct separable from Alzheimers disease, our results provide evidence that this group typically characterized as non-Alzheimers pathologic change or primary age-related tauopathy should be given increased attention, given some similarities in cognitive and biomarker characteristics to groups traditionally considered to be on the Alzheimers continuum.