Characteristics of amyloid‐PET‐negative/tau‐PET‐positive individuals

Background Little is known about tauopathy without β‐amyloid (Aβ) (A‐T+). Since the introduction of the term primary age‐related tauopathy (PART) several clinicopathological studies have revealed the characteristics of this syndrome. We performed this study of people characterized as A‐T+ with PET biomarkers to describe these individuals, and to determine how such individuals did or did not reflect characteristics of AD. Method We included 506 nondemented participants from the ADNI dataset. We used Aβ (18F florbetapir or florbetaben) and tau (18F‐AV1451) PET. We subdivided them into 3 groups (A‐T‐ 324 vs A‐T+ 55 vs A+T+ 127) using predefined thresholds for Aβ (A) and tau (T). We compared these groups by demographics, brain amyloid, brain tau level and distribution, hippocampal volumes, and cognition. Result The A‐T+ group was the oldest among the 3 groups and showed a prevalence of the apolipoprotein E (APOE) ɛ4 genotype similar to A‐T‐ and lower than A+T+. Both the proportion of individuals who were diagnosed with mild cognitive impairment (MCI) and the severity of tau deposition in the A‐T+ group was intermediate between A‐T‐ and A+T+. There was no evidence of even subtly elevated Aβ in the A‐T+ group. A‐T+ showed no asymmetry of tau deposition, and the brain region with the highest tau deposition was the amygdala in both A‐T+ and A+T+ groups (Figure 1). However, the A+T+ group showed a more widespread distribution of tau including temporal, parietal, and occipital areas compared to A‐T+ (Figure 1). Hippocampal volumes (Figure 2) and cognition (Figure 3) were also intermediate to A‐T‐ and A+T+ after adjustment by age, sex, and education. In the A‐T+ group, tau deposition showed a negative association with hippocampal volume and cognition. Conclusion There is no clear evidence that the A‐T+ group is on the AD continuum. Brain Aβ shows no evidence of elevation and APOE genotypes do not show a high prevalence of ɛ4. These individuals are intermediate between A‐T‐ and A+T+ on most characteristics. Such individuals could reflect PART, although longitudinal follow‐up will be necessary to confirm whether any proportion develops overt Aβ‐positive dementia consistent with AD.