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• W2000786089 abstract "Abstract The positron emission tomography ( PET ) ligand 11 C‐labeled Pittsburgh compound B ( PIB ) is used to image β‐amyloid (Aβ) deposits in the brains of living subjects with the intent of detecting early stages of Alzheimer's disease ( AD ). However, deposits of human‐sequence Aβ in amyloid precursor protein transgenic mice and non‐human primates bind very little PIB . The high stoichiometry of PIB :Aβ binding in human AD suggests that the PIB ‐binding site may represent a particularly pathogenic entity and/or report local pathologic conditions. In this study, 3 H‐ PIB was employed to track purification of the PIB ‐binding site in > 90% yield from frontal cortical tissue of autopsy‐diagnosed AD subjects. The purified PIB ‐binding site comprises a distinct, highly insoluble subfraction of the Aβ in AD brain with low buoyant density because of the sodium dodecyl sulfate‐resistant association with a limited subset of brain proteins and lipids with physical properties similar to lipid rafts and to a ganglioside:Aβ complex in AD and Down syndrome brain. Both the protein and lipid components are required for PIB binding. Elucidation of human‐specific biological components and pathways will be important in guiding improvement of the animal models for AD and in identifying new potential therapeutic avenues. image A lipid‐associated subpopulation of Aβ accounts for the high‐affinity binding of Pittsburgh compound B (PIB) in Alzheimer's disease brain. Mass spectrometry of the isolated PIB‐binding site from frontal cortex identified Aβ peptides and a set of plaque‐associated proteins in AD but not age‐matched normal brain. The PIB‐binding site may represent a particularly pathogenic entity and/or report local pathologic conditions." @default.
• W2000786089 created "2016-06-24" @default.
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• W2000786089 date "2014-07-28" @default.
• W2000786089 modified "2023-10-17" @default.
• W2000786089 title "A distinct subfraction of Aβ is responsible for the high-affinity Pittsburgh compound B-binding site in Alzheimer's disease brain" @default.
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• W2000786089 doi "https://doi.org/10.1111/jnc.12815" @default.
• W2000786089 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4205261" @default.
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