Review Article TDP-43 in aging and Alzheimer’s disease – a review
Andrea C. Wilson, Brittany N. Dugger, Dennis W. Dickson, Deng-Shun Wang
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Received October 10, 2010; accepted January, 28, 2011; Epub January 30, 2011; published February 15, 2011
Abstract: Transactive response DNA-binding protein of 43 kDa (TDP-43), an RNA and DNA binding protein involved in transcriptional repression, RNA splicing and RNA metabolism during the stress response, is the major component of neuronal inclusions in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions, now referred to as FTLD TDP. While initially thought to be relatively specific to ALS and FTLD TDP, TDP-43 pathology has now been detected in a number of other neurodegenerative diseases, many associated with tau pathology, including Guam Parkinson dementia complex and Alzheimer’s disease (AD). ITDP-43 pathology is detected in 25% to 50% of AD cases, especially those with more severe clinical phenotype and greater Alzheimer type pathology, as well as AD cases with hippocampal sclerosis (HS). HS is characterized by selective neuronal loss affecting CA1 sector of the hippocampus, and most cases of HS, with or without AD, have TDP-43 pathology. Whether TDP-43 pathology is merely an incidental finding in AD or actually contributing to the more severe clinical phenotype remains unresolved. Presence of TDP-43 in normal elderly, who are at increased risk for AD, would strengthen the argument that it is not merely a secondary or incidental finding in end stage AD. Limited studies suggest that TDP-43 pathology it is infrequent in neurologically normal elderly (3% or less). We provide an overview of what is known about TDP-43 in AD, normal aging and in other disorders and suggest that TDP-43 proteinopathies be considered in two classes – primary and secondary. (IJCEP1010002).
Address all correspondence to: Dr. Deng-Shun Wang University of Wisconsin Department of Pathology and Laboratory Medicine School of Medicine and Public Health 1300 University Avenue (MSC 6330) Madison, WI 53706, USA. Tel: 608-262-9825 E-mail: firstname.lastname@example.org
Dr. Dennis W. Dickson Department of Neuroscience Mayo Clinic, Jacksonville, FL, USA. Tel: 904-953-7137, Fax: 904-953-7117 E-mail: Dickson.Dennis@mayo.edu