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• W2526825314 abstract "Protein aggregates containing β-amyloid (Aβ), phosphorylated tau, and α-synuclein (αSyn) are diagnostic hallmarks of common neurodegenerative diseases. Traditional neuropathological diagnosis of Alzheimer's disease (AD) and Lewy Body Dementia (LBD) relies on semi-quantitative estimation of the density and distribution of amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies (LB). Though historically useful, this approach cannot provide more detailed comparisons between subjects and is fraught with inter-rater variability. This study aims to examine the: (1) correlation between quantitative measures of the triple proteinopathies and their corresponding semi-quantitative staging; and (2) relationship between the proteinopathies. From the Oregon Alzheimer's Disease Center Brain Bank, 220 subjects (68 with normal cognition at death) were selected for having: (1) age at cognitive symptom onset or age at death above 60; (2) available postmortem frozen frontal lobe brain tissue; (3) no missing data or data outside 5 standard deviations from the means; and (4) exclusion of subjects with non-AD tauopathy. Detergent-insoluble proteins were prepared and antibody capture assays were used to quantify α-Syn, Aβ42, Aβ40, amyloid oligomer (AO), Aβ-total, phosphorylated- (p-)tau-396, and tau-total. Histologic examinations of samples were done for conventional assessments of LB, NFT, neuritic plaques (NP), and diffuse plaques (DP) burdens. Multivariate regression analyses, correcting for age at death, duration of illness, and cognitive status, examined the correlation between the quantitative variables and histological stages, and the correlation between different proteinopathies. Quantitative levels of αSyn, Aβ42, Aβ-total, p-tau-396, and tau-total correlated well with their corresponding histological assessments (LB, NP/DP, and NFT), and AO was correlated with NP burden. Presence of LB was not correlated with NP, DP, or NFT burdens (p > 0.05). In contrast, αSyn was significantly associated with AO (p = 0.012) and p-tau-396 (p = 0.002). Quantification of αSyn, Aβ, and p-tau in detergent-insoluble brain proteins correlates well with traditional semi-quantitative staging. It is more sensitive in detecting the relationships between proteinopathies that are not detected by traditional staging and can be a powerful tool for future studies. It provides a more precise and objective measure of proteinopathies in neurodegenerative disease." @default.
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• W2526825314 date "2015-07-01" @default.
• W2526825314 modified "2023-09-27" @default.
• W2526825314 title "P2-182: Quantitative analysis of detergent-insoluble brain proteinaceous aggregates and their correlation with semi-quantitative staging" @default.
• W2526825314 doi "https://doi.org/10.1016/j.jalz.2015.06.721" @default.
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