title: Untangling amyloid-β, tau, and metals in Alzheimer's disease.
abstract: Protein misfolding and metal ion dyshomeostasis are believed to underlie numerous neurodegenerative diseases, including Alzheimer's disease (AD). The pathological hallmark of AD is accumulation of misfolded amyloid-β (Aβ) peptides and hyperphosphorylated tau (ptau) proteins in the brain. Since AD etiology remains unclear, several hypotheses have emerged to elucidate its pathological pathways. The amyloid cascade hypothesis, a leading hypothesis for AD development, advocates Aβ as the principal culprit. Additionally, evidence suggests that tau may contribute to AD pathology. Aβ and tau have also been shown to impact each other's pathology either directly or indirectly. Furthermore, metal ion dyshomeostasis is associated with these misfolded proteins. Metal interactions with Aβ and tau/ptau also influence their aggregation properties and neurotoxicity. Herein, we present current understanding on the roles of Aβ, tau, and metal ions, placing equal emphasis on each of these proposed features, as well as their inter-relationships in AD pathogenesis.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Masha G
authors.initials: MG
authors.lastname: Savelieff
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lim
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D008670:Metals / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008670:Metals; D016875:tau Proteins