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Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease
Open accessAbstract
Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2α (NRXN22α), with their respective postsynaptic functional partners, GluA4‐containing glutamate (AMPA4) receptor and neuroligin 1 (NLGN1), enhance excitatory synaptic activity in some areas of the hippocampus and cerebral cortex. As early damage of such excitatory circuits in the brain tissues of participants with Alzheimer's disease (AD) correlates with cognitive losses, plasma neuron‐derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics. The NDE contents of all 4 proteins were decreased significantly in AD dementia ( n = 46), and diminished levels of AMPA4 and NLGN1 correlated with the extent of cognitive loss. In a preclinical period, 6–11 yr before the onset of dementia, the NDE levels of all but NPTX2 were significantly lower than those of matched controls, and levels of all proteins declined significantly with the development of dementia. Reductions in NDE levels of these specialized excitatory synaptic proteins may therefore be indicative of the extent of cognitive loss and may reflect progression of the severity of AD.—Goetzl, E. J., Abner, E. L., Jicha, G. A., Kapogiannis, D., Schwartz, J. B. Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease. FASEB J. 32, 888–893 (2018). www.fasebj.org
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“A study on plasma neuronal exosomes of patients with AD dementia revealed declined levels of NPTX2 compared with matched controls.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Goetzl et al. 2018
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Metadata
- Authors
- Goetzl, E. J., Abner, E. L., Jicha, G. A., Kapogiannis, D., & Schwartz, J. B.
- Affiliations
- University of California, San Francisco (US)
- University of Kentucky (US)
- National Institute on Aging (US)
- Corresponding author
- Goetzl, Edward J.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2018-01-04
- Volume
- 32
- Issue
- 2
- Pages
- 888-893
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC5888398
- OpenAlex
- W2761598264
- Cited by
- 219
- References
- 28
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 29 · 2023: 27 · 2022: 38 · 2021: 30 · 2020: 21 · 2019: 26 · 2018: 12
- FWCI
- 11.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The FASEB Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P30AG028383)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, plasma biomarkers, NPTX2, neuroligin-1, excitatory synapses, cognitive decline, disease progression, preclinical Alzheimer's disease, synaptic proteins
- MeSH terms
- Pentraxins, Aged, Alzheimer Disease, C-Reactive Protein, Female, Humans, Male, Nerve Tissue Proteins, Neurons, Synaptic Membranes, Cell Adhesion Molecules, Neuronal, Receptors, AMPA, Exosomes
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