Elevated Aβ42 in Skeletal Muscle of Alzheimer Disease Patients Suggests Peripheral Alterations of AβPP Metabolism
Open accessAbstract
The levels of amyloid-beta40 (Abeta40) and Abeta42 peptides were quantified in temporalis muscles and brain of neuropathologically diagnosed Alzheimer disease (AD) and of nondemented individuals. This was achieved by using a novel analytical approach consisting of a combination of fast-performance liquid chromatographic (FPLC) size exclusion chromatography developed under denaturing conditions and europium immunoassay on the 4.0- to 4.5-kd fractions. In the temporalis muscles of the AD and nondemented control groups, the average values for Abeta42 were 15.7 ng/g and 10.2 ng/g (P = 0.010), and for Abeta40 they were 37.8 ng/g and 29.8 ng/g (P = 0.067), respectively. Multiple regression analyses of the AD and control combined populations indicated that 1) muscle Abeta40 and muscle Abeta42 levels were correlated with each other (P < 0.001), 2) muscle Abeta40 levels were positively correlated with age (P = 0. 036), and 3) muscle Abeta42 levels were positively correlated with Braak stage (P = 0.042). Other forms of the Abeta peptide were discovered by mass spectrometry, revealing the presence of Abeta starting at residues 1, 6, 7, 9, 10, and 11 and ending at residues 40, 42, 44, 45, and 46. It is possible that in AD the skeletal muscle may contribute to the elevated plasma pool of Abeta and thus indirectly to the amyloid deposits of the brain parenchyma and cerebral blood vessels. The increased levels of Abeta in the temporalis muscles of AD patients suggest that alterations in AbetaPP and Abeta metabolism may be manifested in peripheral tissues.
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The abundance of muscle-derived amyloid-β increases with age, potentially contributing to amyloid-β deposition in the brain.
“First, the abundance of muscle-derived Aβ increases with age, potentially contributing to Aβ deposition in the brain.292”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [292]
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- Authors
- Kuo, Y.-M., Kokjohn, T. A., Watson, M. D., Woods, A. S., Cotter, R. J., Sue, L. I., Kalback, W. M., Emmerling, M. R., Beach, T. G., & Roher, A. E.
- Affiliations
- Banner Sun Health Research Institute (US)
- Midwestern University (US)
- Johns Hopkins University (US)
- Corresponding author
- Roher, Alex E.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 156
- Issue
- 3
- Pages
- 797-805
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1876838
- OpenAlex
- W2055010339
- Cited by
- 167
- References
- 50
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 7 · 2020: 13 · 2019: 12 · 2018: 4 · 2017: 8 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 3 · 2012: 5
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta 42, Aβ40, skeletal muscle, temporalis muscle, APP processing, Braak stages, plasma amyloid-beta
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Chromatography, High Pressure Liquid, Female, Humans, Immunoenzyme Techniques, Male, Middle Aged, Peptide Fragments, Mass Spectrometry, Temporal Muscle, Blotting, Western, Amyloid beta-Peptides
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