Details

Autor(en) / Beteiligte

• Josephs, Keith A.
• Whitwell, Jennifer L.
• Weigand, Stephen D.
• Murray, Melissa E.
• Tosakulwong, Nirubol
• Liesinger, Amanda M.
• Petrucelli, Leonard
• Senjem, Matthew L.
• Knopman, David S.
• Boeve, Bradley F.
• Ivnik, Robert J.
• Smith, Glenn E.
• Jack, Clifford R.
• Parisi, Joseph E.
• Petersen, Ronald C.
• Dickson, Dennis W.

Titel

TDP-43 is a key player in the clinical features associated with Alzheimer’s disease

Ist Teil von

• Acta neuropathologica, 2014-06, Vol.127 (6), p.811-824

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The aim of this study was to determine whether the TAR DNA-binding protein of 43 kDa (TDP-43) has any independent effect on the clinical and neuroimaging features typically ascribed to Alzheimer’s disease (AD) pathology, and whether TDP-43 pathology could help shed light on the phenomenon of resilient cognition in AD. Three-hundred and forty-two subjects pathologically diagnosed with AD were screened for the presence, burden and distribution of TDP-43. All had been classified as cognitively impaired or normal, prior to death. Atlas-based parcellation and voxel-based morphometry were used to assess regional atrophy on MRI. Regression models controlling for age at death, apolipoprotein ε 4 and other AD-related pathologies were utilized to explore associations between TDP-43 and cognition or brain atrophy, stratified by Braak stage. In addition, we determined whether the effects of TDP-43 were mediated by hippocampal sclerosis. One-hundred and ninety-five (57 %) cases were TDP-positive. After accounting for age, apolipoprotein ε 4 and other pathologies, TDP-43 had a strong effect on cognition, memory loss and medial temporal atrophy in AD. These effects were not mediated by hippocampal sclerosis. TDP-positive subjects were 10× more likely to be cognitively impaired at death compared to TDP-negative subjects. Greater cognitive impairment and medial temporal atrophy were associated with greater TDP-43 burden and more extensive TDP-43 distribution. TDP-43 is an important factor in the manifestation of the clinico-imaging features of AD. TDP-43 also appears to be able to overpower what has been termed resilient brain aging. TDP-43 therefore should be considered a potential therapeutic target for the treatment of AD.