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• W69374983 abstract "Transactive response DNA binding protein 43 (TDP-43) plays a central role in the neuropathology of frontotemporal lobar degeneration and amyotrophic lateral sclerosis, but the relationship between TDP-43 abnormalities and Alzheimer disease (AD) remains unclear. To determine whether TDP-43 can serve as a neuropathologic marker of AD, we performed biochemical characterization and quantification of TDP-43 in homogenates from parietal neocortex of subjects with aclinical diagnosis of no cognitive impairment (NCI, n = 12), mild cognitive impairment (MCI, n = 12), or AD (n = 12). Immunoblots revealed increased detergent-insoluble TDP-43 in the cortex of 0, 3, and 6 of the 12 individuals with NCI, MCI, or AD, respectively. Detergent-insoluble TDP-43 was positively correlated with the accumulation of soluble Aβ42, amyloid plaques, and paired helical filamenttau. In contrast, phospho-TDP-43 was decreased in the cytosolic fraction and detergent-soluble membrane/nuclear fraction from AD patients and correlated with antemortem cognitive function.Immunofluorescence analysis confirmed that the frequencies of individuals with TDP-43 or phospho-TDP-43 cytoplasmic inclusions were higher in AD than in NCI, with MCI at an intermediate level. These data indicate that abnormalities of TDP-43 occur in an important subset of MCI and AD patients and that they correlate with the clinical and neuropathologic features of AD." @default.
• W69374983 created "2016-06-24" @default.
• W69374983 creator A5005670129 @default.
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• W69374983 creator A5022605809 @default.
• W69374983 creator A5022727147 @default.
• W69374983 date "2011-09-01" @default.
• W69374983 modified "2023-10-13" @default.
• W69374983 title "Accumulation of Transactive Response DNA Binding Protein 43 in Mild Cognitive Impairment and Alzheimer Disease" @default.
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• W69374983 doi "https://doi.org/10.1097/nen.0b013e31822c62cf" @default.
• W69374983 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3197017" @default.
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