Cited by 131Alzheimer's disease research and treatmentsAdvanced Glycation End Products researchDementia and Cognitive Impairment Research

Potential implications of endogenous aldehydes in β‐amyloid misfolding, oligomerization and fibrillogenesis

Chen, Kun, Maley, Jason, Yu, Peter H.·2006·Journal of Neurochemistry

Abstract

Aldehydes are capable of inducing protein cross‐linkage. An increase in aldehydes has been found in Alzheimer's disease. Formaldehyde and methylglyoxal are produced via deamination of, respectively, methylamine and aminoacetone catalyzed by semicarbazide‐sensitive amine oxidase (SSAO, EC 1.4.3.6. The enzyme is located on the outer surface of the vasculature, where amyloidosis is often initiated. A high SSAO level has been identified as a risk factor for vascular disorders. Serum SSAO activity has been found to be increased in Alzheimer's patients. Malondialdehyde and 4‐hydroxynonenal are derived from lipid peroxidation under oxidative stress, which is also associated with Alzheimer's disease. Aldehydes may potentially play roles in β‐amyloid aggregation related to the pathology of Alzheimer's disease. In the present study, thioflavin‐T fluorometry, dynamic light scattering, circular dichroism spectroscopy and atomic force microscopy were employed to reveal the effect of endogenous aldehydes on β‐amyloid at different stages, i.e. β‐sheet formation, oligomerization and fibrillogenesis. Formaldehyde, methylglyoxal and malondialdehyde and, to a lesser extent, 4‐hydroxynonenal are not only capable of enhancing the rate of formation of β‐amyloid β‐sheets, oligomers and protofibrils but also of increasing the size of the aggregates. The possible relevance to Alzheimer's disease of the effects of these aldehydes on β‐amyloid deposition is discussed.

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Crossref · 10.1111/j.1471-4159.2006.04181.x

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66 of 66 references verified0 citation errors · 0 not checkable

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  • Various forms of AGEs are markedly aggregated in neuronal plaques in the brain as well as in the serum and cerebrospinal fluid in experimental models and autopsied brains from AD patients compared with controls.

    “Various forms of AGEs are markedly aggregated in neuronal plaques in the brain as well as in the serum and cerebrospinal fluid (CSF) in experimental models and autopsied brains from AD patients compared with the corresponding controls.”
  • Accumulated AGEs can accelerate the formation of Aβ, tau, and APP and induce hyperphosphorylation of tau and cross-linking of AGE-Aβ, leading to an increase in these aggregates.

    “Accumulated AGEs can accelerate the formation of Aβ, tau, and amyloid precursor protein (APP) and induce the hyperphosphorylation of tau and the cross-linking of AGE-Aβ, leading to an increase in these aggregates109.”

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Authors
Chen, K., Maley, J., & Yu, P. H.
Affiliations
University of Saskatchewan (CA)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2006-08-21
Volume
99
Issue
5
Pages
1413-1424
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1993429931
Cited by
131
References
67
Citations by year
2026: 1 · 2025: 13 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 14 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 7 · 2012: 12
FWCI
3.29
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, Alzheimer's disease, protein cross-linking, semicarbazide-sensitive amine oxidase, formaldehyde, methylglyoxal, malondialdehyde, 4-hydroxynonenal, amyloid oligomerization, fibril formation, β-sheet formation, amyloid fibril formation, oxidative stress, lipid peroxidation
MeSH terms
Aldehydes, Alzheimer Disease, Brain, Fluorometry, Formaldehyde, Amine Oxidase (Copper-Containing), Humans, Malondialdehyde, Polymers, Pyruvaldehyde, Spectrum Analysis, Thiazoles, Lipid Peroxidation, Cell Adhesion Molecules, Amyloid beta-Peptides, Neurofibrillary Tangles, Protein Folding, Oxidative Stress, Microscopy, Atomic Force, Proteomics, Benzothiazoles

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