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Review
. 2022 Jul;59(7):4501-4516.
doi: 10.1007/s12035-022-02863-x. Epub 2022 May 17.

The amyloid precursor protein: a converging point in Alzheimer's disease

Alexandré Delport  1 , Raymond Hewer  2
Affiliations
Review

The amyloid precursor protein: a converging point in Alzheimer's disease

Alexandré Delport et al. Mol Neurobiol. 2022 Jul.

Abstract

The decades of evidence that showcase the role of amyloid precursor protein (APP), and its fragment amyloidβ (Aβ), in Alzheimer's disease (AD) pathogenesis are irrefutable. However, the absolute focus on the single APP metabolite Aβ as the cause for AD has resulted in APP and its other fragments that possess toxic propensity, to be overlooked as targets for treatment. The complexity of its processing and its association with systematic metabolism suggests that, if misregulated, APP has the potential to provoke an array of metabolic dysfunctions. This review discusses APP and several of its cleaved products with a particular focus on their toxicity and ability to disrupt healthy cellular function, in relation to AD development. We subsequently argue that the reduction of APP, which would result in a concurrent decrease in Aβ as well as all other toxic APP metabolites, would alleviate the toxic environment associated with AD and slow disease progression. A discussion of those drug-like compounds already identified to possess this capacity is also included.

Keywords: Alzheimer’s disease; Amyloid precursor protein; C-terminal fragment β (CTFβ); C31 peptide; Posiphen.

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References

    1. Van Cauwenberghe C, Van Broeckhoven C, Sleegers K (2016) The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med 18:421–430. https://doi.org/10.1038/gim.2015.117 - DOI - PubMed
    1. Walsh DM, Selkoe DJ (2020) Amyloid β-protein and beyond: the path forward in Alzheimer’s disease. Curr Opin Neurobiol 61:116–124. https://doi.org/10.1016/j.conb.2020.02.003 - DOI - PubMed
    1. Mann D, Davidson YS, Robinson AC, Allen N, Hashimoto T, Richardson A et al (2018) Patterns and severity of vascular amyloid in Alzheimer’s disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer’s disease. Acta Neuropathol 136:569–587. https://doi.org/10.1007/s00401-018-1866-3 - DOI - PubMed - PMC
    1. Patel H, Dobson RJ, Newhouse SJ (2019) A meta-analysis of Alzheimer’s disease brain transcriptomic data. J Alzheimers Dis 68:1635–1656. https://doi.org/10.3233/JAD-181085 - DOI - PubMed - PMC
    1. Moussa-Pacha NM, Abdin SM, Omar HA, Alniss H, Al-Tel TH (2020) BACE1 inhibitors: Current status and future directions in treating Alzheimer’s disease. Med Res Rev 40:339–384. https://doi.org/10.1002/med.21622 - DOI - PubMed

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