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• W1978752470 endingPage "e51" @default.
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• W1978752470 abstract "Background Amyloid-β peptide species ending at positions 40 and 42 (Aβ40, Αβ42) are generated by the proteolytic processing of the Alzheimer's amyloid precursor protein (APP). Aβ peptides accumulate in the brain early in the course of Alzheimer's disease (AD), especially Aβ42. The cytoplasmic domain of APP regulates intracellular trafficking and metabolism of APP and its carboxyl-terminal fragments (CTFα, CTFβ). The role of protein phosphorylation in general, and that of the phosphorylation state of APP at threonine-668 (Thr668) in particular, has been investigated in detail by several laboratories (including our own). Some investigators have recently proposed that the phosphorylation state of Thr668 plays a pivotal role in governing brain Aβ levels, prompting the current study. Methodology In order to evaluate whether the phosphorylation state of Thr668 controlled brain Aβ levels, we studied the levels and subcellular distributions of holoAPP, sAPPα, sAPPβ, CTFα, CTFβ, Aβ40 and Aβ42 in brains from “knock-in” mice in which a non-phosphorylatable alanyl residue had been substituted at position 668, replacing the threonyl residue present in the wild-type protein. Conclusions The levels and subcellular distributions of holoAPP, sAPPα, sAPPβ, CTFα, CTFβ, Aβ40 and Aβ42 in the brains of Thr668Ala mutant mice were identical to those observed in wild-type mice. These results indicate that, despite speculation to the contrary, the phosphorylation state of APP at Thr668 does not play an obvious role in governing the physiological levels of brain Aβ40 or Αβ42 in vivo." @default.
• W1978752470 created "2016-06-24" @default.
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• W1978752470 date "2006-12-20" @default.
• W1978752470 modified "2023-09-29" @default.
• W1978752470 title "Physiological Mouse Brain Aβ Levels Are Not Related to the Phosphorylation State of Threonine-668 of Alzheimer's APP" @default.
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• W1978752470 doi "https://doi.org/10.1371/journal.pone.0000051" @default.
• W1978752470 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1762327" @default.
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