Amyotrophic lateral sclerosis and frontotemporal lobar degeneration: A spectrum of TDP-43 proteinopathies

作者：Geser Felix; Lee Virginia M Y; Trojanowski John Q^*

来源：Neuropathology, 2010, 30(2): 103-112.

DOI：10.1111/j.1440-1789.2009.01091.x

• amyotrophic lateral sclerosis
• frontotemporal lobar degeneration
• multi-system disease
• proteinopathy
• transactive response DNA-binding protein with a Mr of 43 kD (TDP-43)

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.

• 出版日期2010-4