Alzheimer's Amyloidopathy: An Alternative Aspect

Journal of Alzheimer's Disease : JAD
Björn Regland, Andrew McCaddon

Abstract

The 'amyloid hypothesis' dominates Alzheimer's disease (AD) research but has failed to deliver effective therapies. Amyloid precursor protein (APP) and presenilin-1 (PSEN1) genetic mutations are undoubtedly pathogenic, albeit by unclear mechanisms. Conversely, high dose B-vitamins convincingly slow brain atrophy in a pre-stage state of sporadic AD. Here we suggest a link between sporadic and genetic AD: 1) Increased serum homocysteine, a marker of B-vitamin deficiencies, is a significant risk factor for sporadic AD. It also correlates with elevated levels of antichymotrypsin, a serine protease inhibitor. 2) Family members with codon 717 APP mutations and dementia have low serum vitamin B12 values. Overexpression of the APP domain coding for a Kunitz type serine protease inhibitor might explain this. 3) PSEN1 mutations disrupt lysosomal function due to reduced proteolytic activity. They also trap cobalamin (B12) within lysosomes, leading to intracellular deficiency of the vitamin. In summary, APP and PSEN1 mutations both confer a risk for reduced protease activity and B12 bio-availability. Comparably, sporadic AD features a constellation of increased protease inhibition and B-vitamin deficiencies, the central part of which is be...Continue Reading

References

Aug 22, 1992·Lancet·B Regland, C G Gottfries
Oct 1, 1991·Trends in Pharmacological Sciences·J Hardy, D Allsop
Jul 1, 1994·Age and Ageing·A McCaddon, C L Kelly
Feb 22, 2001·Free Radical Biology & Medicine·C A RottkampM A Smith
Jul 17, 2001·Dementia and Geriatric Cognitive Disorders·A McCaddonC Wilkinson
Feb 15, 2002·The New England Journal of Medicine·Sudha SeshadriPhilip A Wolf
May 25, 2005·International Journal of Experimental Pathology·Hyoung-Gon LeeMark A Smith
Apr 4, 2009·Neurobiology of Aging·Dimitri E ZylbersteinIngmar Skoog
Aug 12, 2009·Current Opinion in Chemical Biology·Ruma BanerjeeDominique Padovani
Dec 1, 2010·Expert Reviews in Molecular Medicine·D Sean Froese, Roy A Gravel
Apr 27, 2011·Journal of Neurochemistry·Rima ObeidMarkus Herrmann
Jul 23, 2011·International Journal of Geriatric Psychiatry·Celeste A de JagerA David Smith
Jan 31, 2012·Nature Neuroscience·Iryna BenilovaBart De Strooper
Jun 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nassila AkchicheJean-Luc Daval
Jul 12, 2012·Archives of Biochemistry and Biophysics·Yulia Y StroylovaThomas Haertlé
Mar 30, 2013·The Journal of Biological Chemistry·Carmen GherasimRuma Banerjee
May 22, 2013·Proceedings of the National Academy of Sciences of the United States of America·Gwenaëlle DouaudA David Smith
Aug 29, 2013·Brain : a Journal of Neurology·Babak HooshmandAlina Solomon
Aug 16, 2014·Journal of Alzheimer's Disease : JAD·Hua ZhaoBrett Garner
Jul 20, 2016·Annual Review of Nutrition·A David Smith, Helga Refsum
Aug 11, 2017·Journal of Neurology, Neurosurgery, and Psychiatry·Ka Sing P LaiNathan Herrmann
Feb 27, 2018·Journal of Alzheimer's Disease : JAD·A David SmithRima Obeid

❮ Previous
Next ❯

Citations

Jun 17, 2020·Expert Opinion on Drug Discovery·Dasol KimHo Jeong Kwon
Sep 11, 2021·Reviews in the Neurosciences·Sara MahdiabadiNima Rezaei

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic

Software Mentioned

OPTIMA

Related Concepts

Related Feeds

Alzheimer's Disease: Genetics

Alzheimer's disease is a neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations with this feed.

Alzheimer's Disease: Endosomes

Dysfunctional endosomal trafficking may be associated with Alzheimer’s disease (AD) pathology. Targeting the endosome may advance treatment options for AD. Here is the latest research on endosomes and AD.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Related Papers

Journal of Neurology, Neurosurgery, and Psychiatry
E A CroesC M van Duijn
European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies
M KivipeltoJ Lökk
© 2022 Meta ULC. All rights reserved