From beta amyloid to altered proteostasis in Alzheimer's disease

Ageing Research Reviews
Amalia C BruniCarlo Gabelli

Abstract

Alzheimer's disease (AD) is an age related neurodegenerative disorder causing severe disability and important socio-economic burden, but with no cure available to date. To disentangle this puzzling disease genetic studies represented an important way for the comprehension of pathogenic mechanisms. Abnormal processing and accumulation of amyloid-β peptide (Aβ) has been considered the main cause and trigger factor of the disease. The amyloid cascade theory has fallen into crisis because the failure of several anti-amyloid drugs trials and because of the simple equation AD = abnormal Aβ deposition is not always the case. We now know that multiple neurodegenerative diseases share common pathogenic mechanisms leading to accumulation of misfolded protein species. Genome Wide Association studies (GWAS) led to the identification of large numbers of DNA common variants (SNPs) distributed on different chromosomes and modulating the Alzheimer's risk. GWAS genes fall into several common pathways such as immune system and neuroinflammation, lipid metabolism, synaptic dysfunction and endocytosis, all of them addressing to novel routes for different pathogenic mechanisms. Other hints could be derived from epidemiological and experimental stud...Continue Reading

References

Apr 10, 1992·Science·J A Hardy, G A Higgins
Apr 1, 1991·Neuron·D J Selkoe
Oct 1, 1989·Journal of Neuroimmunology·S ItagakiD Selkoe
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Jan 1, 1988·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·J DavignonC F Sing
Nov 17, 1983·Nature·J F GusellaA Y Sakaguchi
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Dec 1, 1995·Experimental Neurology·E MasliahA D Roses
Jan 1, 1994·Nature Genetics·F SchächterD Cohen
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W J StrittmatterA D Roses
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D E SchmechelA D Roses
Oct 13, 1995·Neuroscience Letters·I GordonD M Michaelson
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·J E DamenG Krystal
Feb 14, 1998·Neuropathology and Applied Neurobiology·T C DicksonJ C Vickers
Jul 11, 1998·Stroke; a Journal of Cerebral Circulation·J ChapmanN M Bornstein
Dec 22, 1999·Neurology·A OttM M Breteler
Dec 28, 1999·Alzheimer Disease and Associated Disorders·P M BretskyV W Henderson
Mar 30, 2000·Annals of Human Genetics·R M Corbo, R Scacchi
Apr 14, 2000·Clinics in Chest Medicine·M G TraberC E Cross
Nov 23, 2000·Lancet·H JickD A Drachman
Aug 2, 2001·The Journal of Experimental Zoology·A E Duggan, I P Callard
Mar 22, 2002·The International Journal of Biochemistry & Cell Biology·Steve E Jones, Catherine Jomary
Jul 27, 2002·Annual Review of Genomics and Human Genetics·Dennis J Selkoe, Marcia B Podlisny
Feb 13, 2003·Archives of Neurology·Martha Clare MorrisRobert S Wilson

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Citations

Feb 10, 2021·The Journal of Pharmacology and Experimental Therapeutics·Zizhen Si, Xidi Wang
May 18, 2021·Frontiers in Aging Neuroscience·Nicolás W MartinezSoledad Matus

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