Deep Profiling of the Aggregated Proteome in Alzheimer’s Disease: From Pathology to Disease Mechanisms
Open accessAbstract
Hallmarks of Alzheimer’s disease (AD), a progressive neurodegenerative disease causing dementia, include protein aggregates such as amyloid beta plaques and tau neurofibrillary tangles in a patient’s brain. Understanding the complete composition and structure of protein aggregates in AD can shed light on the as-yet unidentified underlying mechanisms of AD development and progression. Biochemical isolation of aggregates coupled with mass spectrometry (MS) provides a comprehensive proteomic analysis of aggregates in AD. Dissection of these AD-specific aggregate components, such as U1 small nuclear ribonucleoprotein complex (U1 snRNP), provides novel insights into the deregulation of RNA splicing in the disease. In this review, we summarize the methodologies of laser capture microdissection (LCM) and differential extraction to analyze the aggregated proteomes in AD samples, and discuss the derived novel insights that may contribute to AD pathogenesis.
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Prior aggregated proteome analysis detected deposition of U1 snRNP and a deficit of RNA splicing in AD brain.
“We performed a comprehensive analysis of the aggregated proteome, detecting the deposition of U1 small nuclear ribonucleoprotein (U1 snRNP) and a deficit of RNA splicing in AD brain (Bai et al., 2013; Lutz and Peng, 2018).”
From Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression (2020) · cites this paper as Lutz and Peng, 2018
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- Authors
- Lutz, B. M., & Peng, J.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Peng, Junmin
- ORCID
- Peng, Junmin
- Venue
- Proteomes
- Publisher
- MDPI AG
- Published
- 2018-11-12
- Volume
- 6
- Issue
- 4
- Pages
- 46
- ISSN
- 2227-7382 (ISSN-L)
- PMC
- PMC6313861
- OpenAlex
- W2901636223
- Cited by
- 27
- References
- 87
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 2
- FWCI
- 0.49
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Proteomes (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01AG047928, R01AG053987, R01GM114260)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, protein aggregates, amyloid plaques, neurofibrillary tangles, U1 snRNP, laser capture microdissection, differential extraction, pathogenesis
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