Neurodegenerative biomarkers of A‐T+ compared to A+T+ and A‐T‐ older adults

Abstract

AbstractBackgroundPrimary age‐related tauopathy (PART) is a neuropathological entity with neurofibrillary tangles in the absence of beta‐amyloid plaques in the brain. Recent advances in neuroimaging made it possible to identify amyloid PET‐negative (A‐) tau PET‐positive (T+) condition as a possible candidate for PART in living human brains. We tried to investigate neurodegenerative biomarkers of A‐T+ older adults compared to those of A+T+ and A‐T‐ [corresponding to Alzheimer’s disease (AD) and no AD pathology, respectively] individuals.MethodA total of 156 older participants (64 cognitively normal, 43 mild cognitive impairment (MCI), and 49 dementia), were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). All participants underwent comprehensive clinical evaluation and multimodal brain imaging including amyloid and tau PET, and MRI. Global PiB retention measured by 11C‐PiB‐PET and tau deposition in the regions corresponding to Braak stages measured by 18F‐AV‐1451 PET were used in this study. A+ was defined as global mean Aβ deposition standardized uptake value ratio (SUVR) > 1.4 and T+ was defined as tau burden corresponding to Braak stages I/II, III/IV, or V/VI. Hippocampal volume, AD‐signature cortical thickness (AD‐CT), AD‐signature cerebral glucose metabolism (AD‐CM) and white matter hyperintensity (WMH) volume were also measured as neurodegenerative biomarkers. Multiple linear regression analysis controlling for age, gender, and APOE ε4 positivity was used to investigate the group differences of neurodegenerative biomarkers.ResultOf the 156 participants, 31 were defined as A‐T‐, 53 as A+T‐, and 72 as A+T+. A‐T+ group had higher levels of hippocampal volume (B = 683.448, p<0.001), AD‐CT (B = 0.267, p<0.001) and AD‐CM (B = 0.174, p<0.001), but not WMH volume (B = ‐1.188, p = 0.651), compared to A+T+ group. When compared to A‐T‐ group, A‐T+ group did not show significant difference in any of the neurodegenerative biomarkers.ConclusionOur findings suggest that, in regard of neurodegeneration, older adults with A‐T+ condition, close to pathological PART, are less severe than those with A+T+, while they appear similar to those with A‐T‐.