Tracking disease progression in familial and sporadic frontotemporal lobar degeneration: Recent findings from ARTFL and LEFFTDS

Abstract

Introduction: Familial frontotemporal lobar degeneration (f-FTLD) due to autosomal dominant mutations is an important entity for developing treatments for FTLD. The Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) longitudinal studies were designed to describe the natural history of f-FTLD.

Methods: We summarized recent publications from the ARTFL and LEFFTDS studies, along with other recent publications describing the natural history of f-FTLD.

Results: Published and emerging studies are producing data on all phases of f-FTLD, including the asymptomatic and symptomatic phases of disease, as well as the transitional phase when symptoms are just beginning to develop. These data indicate that rates of change increase along with disease severity, which is consistent with commonly cited models of neurodegeneration, and that measurement of biomarkers may predict onset of symptoms.

Discussion: Data from large multisite studies are producing important data on the natural history of f-FTLD that will be critical for planning intervention trials.

Keywords: C9orf72; GRN; MAPT; familial; frontotemporal lobar degeneration; genetic.

Figure 1

Clinical and neuropathological classification of FTLD. TDP, TAR DNA binding protein 43; FUS, fused in sarcoma; 3R, 3 repeat; 4R, 4 repeat; CBD, corticobasal degeneration; FTDP‐17, frontotemporal dementia Parkinsonism linked to chromosome 17; CTE, chronic traumatic encephalopathy; AGD, argyrophilic grain disease; MST, multisystem tauopathy; see text for additional abbreviations; italicized words are abbreviations for autosomal dominant genes that cause FTLD. (After Seeley et al.)

Figure 2

Theoretical model of disease progression in frontotemporal dementia (FTLD), linking theoretical biomarker changes to clinical stages of illness