In vivo localization of human acetylcholinesterase-derived species in a β-sheet conformation at the core of senile plaques in Alzheimer's disease

The Journal of Biological Chemistry
Létitia JeanDavid J Vaux

Abstract

Many neurodegenerative diseases are characterized by amyloid deposition. In Alzheimer's disease (AD), β-amyloid (Aβ) peptides accumulate extracellularly in senile plaques. The AD amyloid cascade hypothesis proposes that Aβ production or reduced clearance leads to toxicity. In contrast, the cholinergic hypothesis argues for a specific pathology of brain cholinergic pathways. However, neither hypothesis in isolation explains the pattern of AD pathogenesis. Evidence suggests that a connection exists between these two scenarios: the synaptic form of human acetylcholinesterase (hAChE-S) associates with plaques in AD brains; among hAChE variants, only hAChE-S enhances Aβ fibrillization in vitro and Aβ deposition and toxicity in vivo Only hAChE-S contains an amphiphilic C-terminal domain (T40, AChE575-614), with AChE586-599 homologous to Aβ and forming amyloid fibrils, which implicates T40 in AD pathology. We previously showed that the amyloid scavenger, insulin-degrading enzyme (IDE), generates T40-derived amyloidogenic species that, as a peptide mixture, seed Aβ fibrillization. Here, we characterized 11 peptides from a T40-IDE digest for β-sheet conformation, surfactant activity, fibrillization, and seeding capability. We identified...Continue Reading

References

Nov 1, 1992·Neurobiology of Aging·K M ScheggJ H Peacock
Oct 1, 1994·Journal of Neurochemistry·J LiaoU Brodbeck
Jan 1, 1993·Acta Neuropathologica·M A MoránP Gómez-Ramos
Aug 1, 1995·Biophysical Journal·C L Shen, R M Murphy
Dec 1, 1996·Trends in Biochemical Sciences·S B Prusiner
Mar 10, 1999·Journal of Neurology, Neurosurgery, and Psychiatry·P T FrancisG K Wilcock
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·M W WestM H Hecht
Mar 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·D M HoltzmanS M Paul
Jul 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·M SternfeldH Soreq
Mar 7, 2003·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·S Christen-ZaechJ Miklossy
Aug 21, 2003·Neurobiology of Aging·T ReesS Brimijoin
Aug 28, 2003·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Massimo Stefani, Christopher M Dobson
Feb 10, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Matthew G CottinghamDavid J T Vaux
Jun 5, 2004·Ageing Research Reviews·Tibor Kovács
Jul 27, 2004·Protein Science : a Publication of the Protein Society·Sukjoon Yoon, William J Welsh
Sep 14, 2004·Nature Biotechnology·Ana-Maria Fernandez-EscamillaLuis Serrano

❮ Previous
Next ❯

Citations

Dec 12, 2020·Progress in Biophysics and Molecular Biology·Israel Silman

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

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.