The Neuropathology of FTD Associated With ALS : Alzheimer Disease & Associated Disorders (original) (raw)
Original Articles
Department of Pathology, University of British Columbia and Vancouver General Hospital, British Columbia, Canada
Reprints: Dr Ian R. A. Mackenzie, MD, FRCPC, Department of Pathology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, British Columbia, V5Z 1M9 Canada (e-mail: [email protected]).
Abstract
There is increasing recognition of a clinical overlap between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Recent advances in our understanding of the neuropathologic, biochemical, and genetic basis of these conditions provides evidence for a common underlying pathogenesis. The neuropathology in most cases of FTD with ALS is a subtype of frontotemporal lobar degeneration, characterized by neuronal inclusions that are immunoreactive for ubiquitin but not tau (frontotemporal lobar degeneration with ubiquitinated inclusions). These cases show significant pathologic overlap with clinically pure FTD and those with classic ALS. Moreover, the ubiquitinated pathologic protein in all these conditions has recently been identified as TDP-43. A number of families have been reported with autosomal dominant FTD-ALS linked to chromosome 9p and these also have TDP-43–positive frontotemporal lobar degeneration with ubiquitinated inclusions pathology. Together, these findings suggest that FTD-ALS is part of a clinicopathologic spectrum of disease, now identified as TDP-43 proteinopathies.
© 2007 Lippincott Williams & Wilkins, Inc.