Cited by 220Alzheimer's disease research and treatmentsExtracellular vesicles in diseaseDementia and Cognitive Impairment Research

Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease

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Goetzl, Edward J., Abner, Erin L., Jicha, Gregory A., Kapogiannis, Dimitrios, Schwartz, Janice B.·2018·The FASEB Journal

Abstract

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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Crossref · 10.1096/fj.201700731r

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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
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
Locations
  • The FASEB Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (P30AG028383)
Topics
  • Health Sciences › Medicine › Physiology › 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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