Frontotemporal lobar degeneration

Abstract

Frontotemporal lobar degeneration (FTLD) is a diverse group of neurodegenerative diseases associated with variable clinical phenotypes. Most FTLD cases are characterized by the accumulation of abnormal protein inclusions comprised of either TDP-43 or tau and in concert with neuron loss and gliosis of frontal and temporal regions. We describe here the neuropathologic subtypes of FTLD and their corresponding clinical phenotypes. We also highlight the structures and functions of key FTLD-related proteins including C9orf72, TDP-43, progranulin, and tau. Finally, we provide an overview of preclinical studies and clinical trials for the treatment of FTLD and related disorders based on advances in our understanding of the pathophysiology of TDP-43 and tau proteinopathies. Thus, this review highlights the neuropathologic, clinical, and molecular heterogeneity of the FTLD spectrum of diseases that forms the basis for therapeutic development.