Weigand, Stephen D.

See Gordon and Tijms (doi:10.1093/brain/awz278) for a scientific commentary on this article. Jack et al. examine relationships between the bivariate distribution of β-amyloid and tau on PET and established neurocognitive clinical syndromes. Amyloidosis appears to be required for high levels of 3R/4R tau deposition. Whereas abnormal amyloid PET is compatible with normal cognition, highly abnormal tau PET is not.

AbstractIntroductionPrimary age‐related tauopathy (PART) is characterized by the presence of neurofibrillary tangles and absent‐minimal β‐amyloid deposition. Transactive response DNA‐binding protein of 43 kDa (TDP‐43), a third protein, has recently garnished a lot of attention in Alzheimer's disease where it is associated with memory loss and amygdala and hippocampal atrophy. We aimed to determine whether TDP‐43 is associated with brain atrophy in PART.MethodsWe assessed the frequency of TDP‐43 in PART and performed voxel‐level analysis in SPM12, as well as region‐of‐interest analysis using linear regression modeling, controlling for variables of interest, to assess for associations between TDP‐43 and brain atrophy.ResultsOf 116 PART cases, 31 (26.7%) had TDP‐43. The presence of TDP‐43 was associated with significantly greater amygdala, hippocampal, and anterior temporal atrophy in both the region‐of‐interest and the voxel level analyses.DiscussionTDP‐43 is associated with greater brain atrophy in PART.

AbstractIntroductionLittle is known about the role of age on neurodegeneration and protein deposition in atypical variants of Alzheimer's disease (AD).MethodsRegional tau and β‐amyloid positron emission tomography standard uptake value ratios and gray matter volumes were calculated in a cohort of 42 participants with atypical AD. The relationship between regional metrics and age was modeled using a Bayesian hierarchical linear model.ResultsAge was strongly associated with tau uptake across all cortical regions, particularly parietal, with greater uptake in younger participants. Younger age was associated with smaller parietal and lateral temporal volumes. Regional β‐amyloid differed little by age. Age showed a stronger association with tau than volume and β‐amyloid in all cortical regions. Age was not associated with cognitive performance.DiscussionAge is an important determinant of severity of cortical tau uptake in atypical AD, with young participants more likely to show widespread and severe cortical tau uptake.

Despite much attention to the use of biomarkers for predicting Alzheimer disease, little information is available at the individual level. We used the population‐based Mayo Clinic Study of Aging to estimate absolute risk of cognitive impairment by biomarker group. Risk increased with age and any biomarker abnormality. For example, a 75‐year‐old with abnormal amyloid and cortical thinning biomarkers has about a 20% chance of cognitive impairment by age 80 years, whereas with normal biomarkers the chance is <10%. Persons with only one abnormal biomarker had similar intermediate risks. ANN NEUROL 2019;85:155–160.