Advanced glycation end products and protein carbonyl levels in plasma reveal sex-specific differences in Parkinson's and Alzheimer's disease
Open accessAbstract
Neurodegenerative diseases (NDD) such as Alzheimer's (AD) and Parkinson's disease (PD) are distinct clinical entities, however, the aggregation of key neuronal proteins, presumably leading to neuronal demise appears to represent a common mechanism. It has become evident, that advanced glycation end products (AGEs) trigger the accumulation of such modified proteins, which eventually contributes to pathological aspect of NDDs. Increased levels of AGEs are found in amyloid plaques in AD brains and in both advanced and early PD (incidental Lewy body disease). The molecular mechanisms by which AGE dependent modifications may modulate the susceptibility towards NDDs, however, remain enigmatic and it is unclear, whether AGEs may serve as biomarker of NDD. In the present study, we examined AGEs (CML: Carboxymethyllysine and CEL: Carboxyethyllysine), markers of oxidative stress and micronutrients in the plasma of PD and AD patients and controls. As compared to healthy controls, AD females displayed lower levels of CEL while higher levels of CML were found in AD and PD patients. A somewhat similar pattern was observed for protein carbonyls (PC), revealing lower values exclusively in AD females, whereas AD males displayed significantly higher values compared to healthy controls and PD. Sex-specific differences were also observed for other relevant markers such as malondialdehyde, 3-nitrotyrosine, γ -tocopherols, retinol, plasma proteins and α-carotene, while α-tocopherols, β-carotene, lutein/zeaxanthin, β-cryptoxanthin and lycopene showed no relevant association. Taken together, our study suggests yet unappreciated differences of the distribution of AGEs among the sexes in NDD. We therefore suggest to make a clear distinction between sexes when analyzing oxidative (AGEs)-related stress and carbonyl-related stress and vitamins.
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Protein carbonyls are relevant in aging and age-related diseases.
“together indicating the relevance of protein carbonyls in aging and age-related diseases”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
The Introduction describes protein carbonyls as markers of pathological oxidative stress and reports elevated levels in Alzheimer’s and Parkinson’s disease, supporting their relevance to age-related diseases. It calls glycation—not protein carbonylation—age-dependent, and the cited passages do not establish a role for protein carbonyls in aging itself. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredElevated protein carbonyl levels have been found in neurodegenerative disease, such as AD.
“elevated protein carbonyl levels have been found in neurodegenerative disease, such as AD”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
In plasma, protein-bound CML levels were higher in AD patients (n = 40) and PD patients (n = 70) than in controls (n = 34), measured by UPLC-MS/MS.
“| PD and AD | Plasma | Control subjects (n = 34) vs. AD (n = 40) and PD patients (n = 70) | UPLC-MS/MS | Higher protein-bound CML levels in AD and PD patients compared to controls | [151] |”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
MDA levels are lower in elderly male and female AD and PD patients compared to healthy subjects.
“In combination with lower MDA levels in elderly male and female AD and PD patients compared to healthy subjects as well as unchanged concentrations between lung cancer patients and control individuals at advanced age [151,183], this suggests that MDA is no suitable marker for human aging and age-related diseases.”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
Plasma MDA levels are lower in AD patients (n = 40) and PD patients (n = 70) than in control subjects (n = 34), as measured by RP-HPLC.
“| PD and AD | Plasma | Control subjects (n = 34) vs. AD (n = 40) and PD patients (n = 70) | RP-HPLC | Lower MDA levels in AD and PD patients compared to control subjects | [151] |”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
MDA is not a suitable marker for human aging and age-related diseases.
“In combination with lower MDA levels in elderly male and female AD and PD patients compared to healthy subjects as well as unchanged concentrations between lung cancer patients and control individuals at advanced age [151,183], this suggests that MDA is no suitable marker for human aging and age-related diseases.”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
Sharma et al. found lower MDA levels in AD and PD patients compared to controls using reversed-phase HPLC with fluorescence detection.
“Reversed-phase HPLC coupled with fluorescence detection has been further used by Sharma and colleagues, revealing lower levels of MDA in AD and PD patients compared to controls [151].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
In male AD patients, 3-NT levels are higher compared to PD patients and controls (plasma, ELISA).
“Higher 3-NT levels in male AD patients compared to PD patients and controls”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [151]
The amounts of plasma AGEs, which can stimulate the aggregation of specifically modified proteins, are different in Alzheimer's and Parkinson's disease patients in a sex-dependent manner.
“However, the amounts of plasma AGEs, which can stimulate the aggregation of specifically modified proteins, are different in Alzheimer’s and Parkinson’s disease patients in a sex-dependent manner, thus requiring a careful interpretation of test results104.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [104]
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- Authors
- Sharma, A., Weber, D., Raupbach, J., Dakal, T. C., Fließbach, K., Ramirez, A., Grune, T., & Wüllner, U.
- Affiliations
- University Hospital Bonn (DE)
- German Institute of Human Nutrition (DE)
- Mohanlal Sukhadia University (IN)
- Corresponding author
- Wüllner, Ullrich
- ORCID
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 34
- Pages
- 101546
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC7251371
- OpenAlex
- W3025144071
- Cited by
- 120
- References
- 37
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 20 · 2023: 22 · 2022: 18 · 2021: 26 · 2020: 1
- FWCI
- 11.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DZNE Pub (submittedVersion, other-oa)
- Funders
- German Federal Ministry of Education and Research (# 01KU1403B)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- advanced glycation end products, protein carbonyls, Parkinson's disease, Alzheimer's disease, sex differences, carboxymethyllysine, oxidative stress, neurodegenerative diseases, biomarkers, vitamin E, malondialdehyde, nitrotyrosine, retinol, carotenoids
- MeSH terms
- Alzheimer Disease, Female, Humans, Male, Parkinson Disease, Glycation End Products, Advanced, Protein Carbonylation
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