Tau heterogeneity in Aβ positive patients

Abstract

AbstractBackgroundA substantial proportion of individuals on the AD continuum have tau PET burden that is not elevated, suggesting that they may be in an earlier stage on the AD continuum and/or have other copathologies that account for their impairment. To examine these possibilities, we compared Aβ+, cognitively impaired individuals with lower tau burden to theirAβ+ high tau counterparts across a variety of biomarker and clinical measurements.MethodWe identified Aβ+, impaired (MCI or AD) patients from ADNI with high and low tau burden using contemporaneous amyloid PET (florbetapir or florbetaben) and tau PET (flortaucipir) scans. The high/low tau threshold was the 90th percentile SUVr of Aβ‐ cognitively normal individuals for a composite flortaucipir region of interest spanning most of the medial/lateral temporal lobes and extratemporal neocortex relative to inferior cerebellar grey matter (Figure 1). We compared Aβ+ high vs low tau groups on AD/cerebrovascular biomarkers, and demographic, cognitive, risk factor, and clinical measurements.ResultOf 218 Aβ+ impaired ADNI patients, 91 (42%) had cortical tau in the normal range. Compared to their high tau counterparts, low tau individuals were more likely to be male, older, have more years of education, and lower Aβ (within the elevated/abnormal range), but did not differ on proportion of ApoE4 carriers. Low tau individuals were also more likely to have cardiovascular risk factors and cerebrovascular pathology, but had less severe hippocampal atrophy and temporoparietal hypometabolism and better cognitive performance than high tau individuals. Examination of baseline tau (Figure 2A) and longitudinal tau (Figure 2B) rankings across 70 FreeSurfer‐defined regions revealed a highly overlapping set of medial/lateral temporal regions common to both high/low groups.ConclusionFor impaired individuals on the AD pathway, low tau PET burden is associated with heterogeneous group characteristics that support a role for copathologies in accounting for cognitive symptoms, but also point to the less advanced stage of cognitive and biomarker progression in this group. Despite these striking group differences, the set of regions in which tau was highest in the brain was strikingly consistent between groups, suggesting a common spatial accumulation pattern regardless of the degree of tau burden.