Brain atrophy in primary age-related tauopathy is linked to transactive response DNA-binding protein of 43 kDa

Introduction: Primary 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. Methods: We 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. Results: Of 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. Discussion: TDP-43 is associated with greater brain atrophy in PART.