Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration: a Spectrum of TDP-43 Proteinopathies

Overview

Journal Neuropathology

Specialties Neurology
Pathology

Date 2010 Jan 28

PMID 20102519

Citations 101

Authors

Felix Geser

Virginia M-Y Lee

John Q Trojanowski

Affiliations

Soon will be listed here.

Abstract

It is now established that pathological transactive response DNA-binding protein with a Mr of 43 kD (TDP-43) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis is the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitin-positive inclusions (now known as FTLD-TDP). In fact, the discovery of pathological TDP-43 solidified the idea that these disorders are multi-system diseases and this led to the concept of a TDP-43 proteinopathy as a spectrum of disorders comprised of different clinical and pathological entities extending from ALS to ALS with cognitive impairment/dementia and FTLD-TDP without or with motor neuron disease (FTLD-MND). These align along a broad disease continuum sharing similar pathogenetic mechanisms linked to pathological TDP-43. We here review salient findings in the development of a concept of TDP-43 proteinopathy as a novel group of neurodegenerative diseases similar in concept to alpha-synucleinopathies and tauopathies.

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