Potential implications of endogenous aldehydes in β‐amyloid misfolding, oligomerization and fibrillogenesis
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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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.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [109]
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.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [109]
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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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