Petersen, R. C.

Transactive response DNA-binding protein of 43 kDa (TDP-43) type-A is associated with frontotemporal lobar degeneration (FTLD). In primary age-related tauopathy (PART), TDP-type-α displays similar features to FTLD-TDP type-A. We compared antemortem MRI volumes of amygdala nuclei and hippocampal subfields between 16 PART-TDP-α and 12 FTLD-TDP-A autopsy-confirmed cases. Hippocampal tail and CA1 body volumes were smaller in PART-TDP-α group, which also had smaller lateral and central amygdala nuclei compared to FTLD-TDP-A group, but differences were non-significant after FDR correction. There is no evidence suggesting that TDP-43 type-A in FTLD affects hippocampal and amygdala volume loss differently than TDP-43 type-α in PART.

Background and purposeThe aim of our study was to determine the utility of longitudinal magnetic resonance imaging (MRI) measurements as potential biomarkers in the main genetic variants of frontotemporal dementia (FTD), including microtubule‐associated protein tau (MAPT) and progranulin (GRN) mutations and C9ORF72 repeat expansions, as well as sporadic FTD.MethodsIn this longitudinal study, 58 subjects were identified who had at least two MRI and MAPT mutations (n = 21), GRN mutations (n = 11), C9ORF72 repeat expansions (n = 11) or sporadic FTD (n = 15). A total of 198 serial MRI measurements were analyzed. Rates of whole brain atrophy were calculated using the boundary shift integral. Regional rates of atrophy were calculated using tensor‐based morphometry. Sample size estimates were calculated.ResultsProgressive brain atrophy was observed in all groups, with fastest rates of whole brain atrophy in GRN, followed by sporadic FTD, C9ORF72 and MAPT. All variants showed greatest rates in the frontal and temporal lobes, with parietal lobes also strikingly affected in GRN. Regional rates of atrophy across all lobes were greater in GRN compared to the other groups. C9ORF72 showed greater rates of atrophy in the left cerebellum and right occipital lobe than MAPT, and sporadic FTD showed greater rates in the anterior cingulate than C9ORF72 and MAPT. Sample size estimates were lowest using temporal lobe rates in GRN, ventricular rates in MAPT and C9ORF72, and whole brain rates in sporadic FTD.ConclusionThese data support the utility of using rates of atrophy as outcome measures in future drug trials in FTD and show that different imaging biomarkers may offer advantages in the different variants of FTD.