TDP‐43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing

• Published in: Brain pathology (Zurich, Switzerland) Vol. 27; no. 4; pp. 472 - 479
• Main Authors: McAleese, Kirsty E., Walker, Lauren, Erskine, Daniel, Thomas, Alan J., McKeith, Ian G., Attems, Johannes
• Format: Journal Article
• Language: English
• Published: Switzerland John Wiley & Sons, Inc 01.07.2017; John Wiley and Sons Inc
• Subjects: Age; Aged; Aged, 80 and over; ageing; Aging; Aging - pathology; Alzheimer Disease - complications; Alzheimer Disease - pathology; Alzheimer's disease; Amygdala; Antibodies; Binding; Brain - metabolism; Brain - pathology; Cognition Disorders - etiology; Death; Dementia; Dementia disorders; dementia with Lewy bodies; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - metabolism; Female; Genes; hippocampal sclerosis; Hippocampus; Humans; Inclusions; Intracellular; Lewy bodies; Lewy Body Disease - complications; Lewy Body Disease - pathology; Lewy body diseases; Male; mixed Alzheimer's disease and dementia with Lewy bodies; Neocortex; Neostriatum; Neurodegeneration; Neurodegenerative diseases; Neuropsychological Tests; Paraffin; Pathology; Psychiatric Status Rating Scales; TDP‐43; dementia with Lewy bodies; ageing; TDP-43; hippocampal sclerosis; Lewy body diseases; Alzheimer's disease; mixed Alzheimer's disease and dementia with Lewy bodies
• ISSN: 1015-6305; 1750-3639
• DOI: 10.1111/bpa.12424

Intracellular inclusions consisting of TAR DNA binding protein‐43 (TDP‐43 pathology) are present in up to 57% of Alzheimer's disease (AD) cases and follow a distinct topographical pattern of progression described in the TDP‐43 in AD staging scheme. This scheme has not been applied to the assessment of TDP‐43 pathology in dementia with Lewy bodies (DLB) and aged controls. We investigated TDP‐43 pathology prevalence and severity in AD, DLB, mixed AD/DLB (Mx AD/DLB) and aged controls. One hundred and nineteen human post‐mortem brains were included, neuropathologically diagnosed as AD: 46, DLB: 15, Mx AD/DLB: 19 and aged controls: 39. Paraffin sections inclusive of the amygdala, hippocampus, striatum and neocortex were immunohistochemically stained with antibodies against phosphorylated TDP‐43 and staged according to the TDP‐43 in AD staging scheme. TDP‐43 pathology was present in all groups: AD: 73.9%, DLB: 33.3%, Mx AD/DLB: 52.6% and controls: 17.9%. Prevalence of TDP‐43 pathology was significantly higher in AD and Mx AD/DLB compared to controls. In controls, higher age at death was associated with prevalence of TDP‐43 pathology and higher TDP‐43 in AD stage, suggesting that this type of TDP‐43 pathology may partly be an age‐associated phenomenon. Significantly higher prevalence of TDP‐43 pathology in the AD group indicates that AD pathology possibly triggers and aggravates TDP‐43 pathology. The validity of the TDP‐43 in AD staging scheme is not limited to AD and should be applied to assess TDP‐43 pathology in post mortem brains of aged individuals to further elucidate the role of TDP‐43 pathology in age associated neurodegeneration.