Amyotrophic lateral sclerosis features predict TDP-43 pathology in frontotemporal lobar degeneration

Clinical and pathological heterogeneity is common in patients with frontotemporal lobar degeneration (FTLD) pathology. This investigated clinical or imaging characteristics that differentiate FTLD-TDP from FTLD-tau, FTLD-TDP subtypes from each other, or pathological stages of FTLD-TDP. Initial clinical, neu-ropsychological and neuroimaging characteristics were compared between pathologically defined FTLD-tau and FTLD-TDP groups. Voxel-based morphometry analyses contrasted grey matter atrophy patterns. Twenty-six FTLD-TDP, 28 FTLD-tau and 78 controls were included. Amyotrophic lateral sclerosis features, when present, were highly specific FTLD-TDP, which displayed greater cortical and subcortical atrophy than FTLD-tau. FTLD-TDP-43 type B had significantly shorter survival than type A. Type A patients were more cognitively impaired than type B, and basal ganglia atrophy appeared to distinguish type A from type B. Age at onset and survival duration were comparable between stages II and IV. In conclusion, Amy-otrophic lateral sclerosis features may be useful in distinguishing FTLD-TDP from FTLD-tau. TDP-43 type A and B appear to present with distinct profiles. The relationship between clinical features and pathological staging in FTLD-TDP-43 is complex, and TDP-43 subtyping may have more clinical utility. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

Clinical and pathological heterogeneity is common in patients with frontotemporal lobar degeneration (FTLD) pathology. Characteristics that differentiate between FTLD-TDP and FTLD-tau, as well as different subtypes within FTLD-TDP, were investigated. Amyotrophic lateral sclerosis features were highly specific for FTLD-TDP, which showed greater atrophy than FTLD-tau. TDP-43 subtyping may have more clinical utility in distinguishing different profiles within FTLD-TDP.