Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease
- PMID: 18218341
- PMCID: PMC3107703
- DOI: 10.1016/j.molmed.2007.12.002
Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease
Abstract
Recent studies of postmortem brains from Alzheimer's disease (AD) patients and transgenic mouse models of AD suggest that oxidative damage, induced by amyloid beta (Abeta), is associated with mitochondria early in AD progression. Abeta and amyloid-precursor protein are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron-transport chain, increase reactive oxygen species production, cause mitochondrial damage and prevent neurons from functioning normally. Furthermore, accumulation of Abeta at synaptic terminals might contribute to synaptic damage and cognitive decline in patients with AD. Here, we describe recent studies regarding the roles of Abeta and mitochondrial function in AD progression and particularly in synaptic damage and cognitive decline.
Figures



Similar articles
-
Amyloid-beta and mitochondria in aging and Alzheimer's disease: implications for synaptic damage and cognitive decline.J Alzheimers Dis. 2010;20 Suppl 2(Suppl 2):S499-512. doi: 10.3233/JAD-2010-100504. J Alzheimers Dis. 2010. PMID: 20413847 Free PMC article. Review.
-
Inhibition of Drp1 Ameliorates Synaptic Depression, Aβ Deposition, and Cognitive Impairment in an Alzheimer's Disease Model.J Neurosci. 2017 May 17;37(20):5099-5110. doi: 10.1523/JNEUROSCI.2385-16.2017. Epub 2017 Apr 21. J Neurosci. 2017. PMID: 28432138 Free PMC article.
-
Regulation of Synaptic Amyloid-β Generation through BACE1 Retrograde Transport in a Mouse Model of Alzheimer's Disease.J Neurosci. 2017 Mar 8;37(10):2639-2655. doi: 10.1523/JNEUROSCI.2851-16.2017. Epub 2017 Feb 3. J Neurosci. 2017. PMID: 28159908 Free PMC article.
-
Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression.Hum Mol Genet. 2006 May 1;15(9):1437-49. doi: 10.1093/hmg/ddl066. Epub 2006 Mar 21. Hum Mol Genet. 2006. PMID: 16551656
-
Synaptic Mitochondria: An Early Target of Amyloid-β and Tau in Alzheimer's Disease.J Alzheimers Dis. 2021;84(4):1391-1414. doi: 10.3233/JAD-215139. J Alzheimers Dis. 2021. PMID: 34719499 Review.
Cited by
-
Lithium Benzoate Exerts Neuroprotective Effect by Improving Mitochondrial Function, Attenuating Reactive Oxygen Species, and Protecting Cognition and Memory in an Animal Model of Alzheimer's Disease.J Alzheimers Dis Rep. 2022 Sep 20;6(1):557-575. doi: 10.3233/ADR-220025. eCollection 2022. J Alzheimers Dis Rep. 2022. PMID: 36275418 Free PMC article.
-
Incorporation of β-sitosterol into mitochondrial membrane enhances mitochondrial function by promoting inner mitochondrial membrane fluidity.J Bioenerg Biomembr. 2013 Jun;45(3):301-5. doi: 10.1007/s10863-012-9495-3. Epub 2012 Dec 8. J Bioenerg Biomembr. 2013. PMID: 23225137
-
Polyphenols as Potential Metal Chelation Compounds Against Alzheimer's Disease.J Alzheimers Dis. 2021;82(s1):S335-S357. doi: 10.3233/JAD-200185. J Alzheimers Dis. 2021. PMID: 32568200 Free PMC article. Review.
-
Relationships between Mitochondrial Dysfunction and Neurotransmission Failure in Alzheimer's Disease.Aging Dis. 2020 Oct 1;11(5):1291-1316. doi: 10.14336/AD.2019.1125. eCollection 2020 Oct. Aging Dis. 2020. PMID: 33014538 Free PMC article. Review.
-
Alzheimer's Disease Pathology and Assistive Nanotheranostic Approaches for Its Therapeutic Interventions.Int J Mol Sci. 2024 Sep 7;25(17):9690. doi: 10.3390/ijms25179690. Int J Mol Sci. 2024. PMID: 39273645 Free PMC article. Review.
References
-
- Manczak M, et al. Mitochondria are a direct site of Abeta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet. 2006;15:1437–1449. - PubMed
-
- Caspersen C, et al. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J. 2005;19:2040–1. - PubMed
-
- Nunomura A, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60:759–767. - PubMed
-
- Selkoe DJ. Alzheimer's disease is a synaptic failure. Science. 2002;298:789–791. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical