» Articles » PMID: 39697643

Physiopathological Mechanisms Underlying Alzheimer's Disease: a Narrative Review

Overview
Date 2024 Dec 19
PMID 39697643
Authors
Affiliations
Soon will be listed here.
Abstract

The neuropathological signature of Alzheimer's disease (AD) comprises mainly amyloid plaques, and neurofibrillary tangles, resulting in synaptic and neuronal loss. These pathological structures stem from amyloid dysfunctional metabolism according to the amyloid cascade hypothesis, leading to the formation of plaques, and apparently inducing the initiation of the abnormal tau pathway, with phosphorylation and aggregation of these proteins, ultimately causing the formation of tangles. In this narrative review, the existing hypothesis related to the pathophysiology of AD were compiled, and biological pathways were highlighted in order to identify the molecules that could represent biological markers of the disease, necessary to establish early diagnosis, as well as the selection of patients for therapeutical interventional strategies.

References
1.
Chen G, Xu T, Yan Y, Zhou Y, Jiang Y, Melcher K . Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017; 38(9):1205-1235. PMC: 5589967. DOI: 10.1038/aps.2017.28. View

2.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan E . Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34(7):939-44. DOI: 10.1212/wnl.34.7.939. View

3.
Selkoe D . Amyloid beta-protein and the genetics of Alzheimer's disease. J Biol Chem. 1996; 271(31):18295-8. DOI: 10.1074/jbc.271.31.18295. View

4.
Belyaev N, Kellett K, Beckett C, Makova N, Revett T, Nalivaeva N . The transcriptionally active amyloid precursor protein (APP) intracellular domain is preferentially produced from the 695 isoform of APP in a {beta}-secretase-dependent pathway. J Biol Chem. 2010; 285(53):41443-54. PMC: 3009870. DOI: 10.1074/jbc.M110.141390. View

5.
Bhat A, Dar K, Anees S, Zargar M, Masood A, Sofi M . Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother. 2015; 74:101-10. DOI: 10.1016/j.biopha.2015.07.025. View