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Cited by 174Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAdvanced Proteomics Techniques and Applications

Compilation of reported protein changes in the brain in Alzheimer's disease

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Askenazi, Manor, Kavanagh, Tomas, Pires, Geoffrey, Ueberheide, Beatrix, Wisniewski, Thomas, Drummond, Eleanor·2023·Nature Communications
DOI 10.1038/s41467-023-40208-xPMC PMC10368642
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Abstract

Proteomic studies of human Alzheimer’s disease brain tissue have potential to identify protein changes that drive disease, and to identify new drug targets. Here, we analyse 38 published Alzheimer’s disease proteomic studies, generating a map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical Alzheimer’s disease, mild cognitive impairment, advanced Alzheimer’s disease), and proteins enriched in amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy. Our dataset is compiled into a searchable database (NeuroPro). We found 848 proteins were consistently altered in 5 or more studies. Comparison of protein changes in early-stage and advanced Alzheimer’s disease revealed proteins associated with synapse, vesicle, and lysosomal pathways show change early in disease, but widespread changes in mitochondrial associated protein expression change are only seen in advanced Alzheimer’s disease. Protein changes were similar for brain regions considered vulnerable and regions considered resistant. This resource provides insight into Alzheimer’s disease brain protein changes and highlights proteins of interest for further study.

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  • Proteomic PPI networks in CA1, CA2, and subiculum showed increased abundance of proteins involved in glial activation, neutrophil degranulation, leukocyte adhesion, complement C1q complexes, and RAC-NOX2-mediated inflammatory signaling supporting proteomics findings in DS-AD and other subtypes of AD.

    “Moreover, proteomic PPI networks in CA1, CA2, and subiculum showed increased abundance of proteins involved in glial activation, neutrophil degranulation, leukocyte adhesion, complement C1q complexes, and RAC–NOX2–mediated inflammatory signaling supporting proteomics findings in DS‐AD and other subtypes of AD. 51 , 63”

    From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [63]

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References 78 · Cited by 174

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Authors
Askenazi, M., Kavanagh, T., Pires, G., Ueberheide, B., Wisniewski, T., & Drummond, E.
Affiliations
  • The University of Sydney (AU)
  • New York University (US)
Corresponding author
Drummond, Eleanor
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-07-25
Volume
14
Issue
1
Pages
4466-4466
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-40208-x
PMC
PMC10368642
OpenAlex
W4385231422
Cited by
174
References
78
Citations by year
2026: 45 · 2025: 83 · 2024: 40 · 2023: 6
FWCI
31.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Alzheimer’s Association (Blas Frangione Early Career Award)
  • Department of Health | National Health and Medical Research Council (1132524)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
Alzheimer's disease, brain proteome, protein expression changes, amyloid plaques, neurofibrillary tangles, cerebral amyloid angiopathy, mild cognitive impairment, preclinical Alzheimer's disease, disease stage, synapses, vesicle trafficking, lysosomes, mitochondrial proteins, therapeutic target
MeSH terms
Alzheimer Disease, Brain, Humans, Proteins, Amyloid beta-Peptides, Neurofibrillary Tangles, Proteomics, Protein Interaction Maps

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