title: TDP-43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing.
abstract: 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.
authors: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors: Kirsty E
authors: KE
authors: McAleese
authors: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors: Lauren
authors: L
authors: Walker
authors: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors: Daniel
authors: D
authors: Erskine
authors: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors: Alan J
authors: AJ
authors: Thomas
authors: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors: Ian G
authors: IG
authors: McKeith
authors: Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.
authors: Johannes
authors: J
authors: Attems
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000473:pathology*; D008297:Male; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human
keywords: Alzheimer's disease; Lewy body diseases; TDP-43; ageing; dementia with Lewy bodies; hippocampal sclerosis; mixed Alzheimer's disease and dementia with Lewy bodies