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

Edward J. Goetzl; Erin L. Abner; Gregory A. Jicha; Dimitrios Kapogiannis; Janice B. Schwartz

doi:10.1096/fj.201700731R

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

Edward J. Goetzl, Erin L. Abner, Gregory A. Jicha, Dimitrios Kapogiannis, Janice B. Schwartz

Research output: Contribution to journal › Article › peer-review

186 Scopus citations

Abstract

Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2a (NRXN2a), 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 participantswithAlzheimer's disease (AD) correlateswith cognitive losses, plasmaneuron-derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics. TheNDE contents of all 4 proteinswere decreased significantly inADdementia (n=46), anddiminished levels ofAMPA4andNLGN1 correlatedwiththe extent of cognitive loss. In a preclinical period, 6-11 yr before the onset of dementia, theNDE levels of all butNPTX2were significantly lower than those ofmatched controls, and levels of all proteins declined significantly with the development of dementia. Reductions inNDE levels of these specialized excitatory synaptic proteinsmay 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.

Original language	English
Pages (from-to)	888-893
Number of pages	6
Journal	FASEB Journal
Volume	32
Issue number	2
DOIs	https://doi.org/10.1096/fj.201700731R
State	Published - Feb 2018

Bibliographical note

Publisher Copyright:
© FASEB.

Funding

The authors thank Judith H. Goetzl (Jewish Home of San Francisco) for expert preparation of the illustrations. This work was supported by a grant from the Biomarkers Across Neurodegenerative Diseases 2 (BAND2) program of the Michael J. Fox Foundation for Parkinson’s Research, the Alzheimer’s Association, Alzheimer’s Research United Kingdom, and the Weston Brain Institute (to E.J.G.); and by the U.S. National Institutes of Health (NIH) National Institute on Aging (NIA) (Grant P30028383; to G.A.J.). D.K. was supported by the Intramural Research Program of the NIH NIA. E.J.G. has filed an application with the U.S. Patent Office for the platform and methodologies described in this report. The remaining authors declare no conflicts of interest.

Funders	Funder number
Alzheimer’s Research United Kingdom
ARUK Biomarkers Across Neurodegenerative Diseases
NIA/NIH
National Institutes of Health (NIH)
National Institute on Aging	P30AG028383, P30028383
National Institute on Aging
Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment
Weston Brain Institute

Keywords

Biomarkers
Dementia
Neurodegeneration

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Genetics

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10.1096/fj.201700731R

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abstract = "Interactions of the presynaptic proteins, neuronal pentraxin 2 (NPTX2) and neurexin 2a (NRXN2a), 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 participantswithAlzheimer's disease (AD) correlateswith cognitive losses, plasmaneuron-derived exosome (NDE) levels of these 2 pairs of specialized synaptic proteins were quantified to assess their biomarker characteristics. TheNDE contents of all 4 proteinswere decreased significantly inADdementia (n=46), anddiminished levels ofAMPA4andNLGN1 correlatedwiththe extent of cognitive loss. In a preclinical period, 6-11 yr before the onset of dementia, theNDE levels of all butNPTX2were significantly lower than those ofmatched controls, and levels of all proteins declined significantly with the development of dementia. Reductions inNDE levels of these specialized excitatory synaptic proteinsmay 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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Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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