Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A : Biomarkers of synaptic density in Alzheimer's disease

Mecca, Adam P. ; Ashton, Nicholas J. ; Chen, Ming Kai ; O'Dell, Ryan S. ; Toyonaga, Takaya ; Zhao, Wenzhen ; Young, Juan J. ; Salardini, Elaheh ; Bates, Kara A. and Ra, Jocelyn , et al. (2025) In Alzheimer's and Dementia 21(6).
Abstract

INTRODUCTION: Positron emission tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer's disease (AD). We investigated associations between SV2A concentrations in the brain and cerebrospinal fluid (CSF). METHODS: Twenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [11C]UCB-J PET. We used a novel enzyme-linked immunosorbent assay (ELISA) to measure CSF SV2A. Other synaptic and axonal proteins were also measured in CSF. RESULTS: CSF SV2A was lower in AD compared to CN participants. Within the AD group, CSF SV2A was highly correlated with SV2A PET. By contrast, other CSF proteins... (More)

INTRODUCTION: Positron emission tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer's disease (AD). We investigated associations between SV2A concentrations in the brain and cerebrospinal fluid (CSF). METHODS: Twenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [11C]UCB-J PET. We used a novel enzyme-linked immunosorbent assay (ELISA) to measure CSF SV2A. Other synaptic and axonal proteins were also measured in CSF. RESULTS: CSF SV2A was lower in AD compared to CN participants. Within the AD group, CSF SV2A was highly correlated with SV2A PET. By contrast, other CSF proteins were generally higher in participants with AD and not associated with SV2A PET. DISCUSSION: We report a novel CSF assay for SV2A that is strongly correlated with the PET measurement of SV2A. Our results suggest that CSF SV2A may serve as a biomarker for synaptic density in AD. Highlights: Synaptic vesicle glycoprotein 2A (SV2A) measured by a novel cerebrospinal fluid (CSF) enzyme-linked immunosorbent assay (ELISA) was lower in participants with symptomatic Alzheimer's disease (AD). CSF SV2A was highly correlated with SV2A measured by positron emission tomography (PET) in participants with AD. Other CSF synaptic/axonal proteins were not significantly associated with SV2A PET. CSF SV2A may serve as a biomarker for synaptic density in AD.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, biomarkers, CSF, SV2A, synaptic density
in
Alzheimer's and Dementia
volume
21
issue
6
article number
e70344
publisher
Wiley
external identifiers
  • pmid:40491249
  • scopus:105008334959
ISSN
1552-5260
DOI
10.1002/alz.70344
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
id
d701dc59-6180-407c-88a0-52081e0e5336
date added to LUP
2025-12-29 13:54:40
date last changed
2025-12-29 13:55:44
@article{d701dc59-6180-407c-88a0-52081e0e5336,
  abstract     = {{<p>INTRODUCTION: Positron emission tomography (PET) imaging with ligands for synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising methodology for measuring synaptic density in Alzheimer's disease (AD). We investigated associations between SV2A concentrations in the brain and cerebrospinal fluid (CSF). METHODS: Twenty-one participants with early AD and 7 cognitively normal (CN) individuals underwent [<sup>11</sup>C]UCB-J PET. We used a novel enzyme-linked immunosorbent assay (ELISA) to measure CSF SV2A. Other synaptic and axonal proteins were also measured in CSF. RESULTS: CSF SV2A was lower in AD compared to CN participants. Within the AD group, CSF SV2A was highly correlated with SV2A PET. By contrast, other CSF proteins were generally higher in participants with AD and not associated with SV2A PET. DISCUSSION: We report a novel CSF assay for SV2A that is strongly correlated with the PET measurement of SV2A. Our results suggest that CSF SV2A may serve as a biomarker for synaptic density in AD. Highlights: Synaptic vesicle glycoprotein 2A (SV2A) measured by a novel cerebrospinal fluid (CSF) enzyme-linked immunosorbent assay (ELISA) was lower in participants with symptomatic Alzheimer's disease (AD). CSF SV2A was highly correlated with SV2A measured by positron emission tomography (PET) in participants with AD. Other CSF synaptic/axonal proteins were not significantly associated with SV2A PET. CSF SV2A may serve as a biomarker for synaptic density in AD.</p>}},
  author       = {{Mecca, Adam P. and Ashton, Nicholas J. and Chen, Ming Kai and O'Dell, Ryan S. and Toyonaga, Takaya and Zhao, Wenzhen and Young, Juan J. and Salardini, Elaheh and Bates, Kara A. and Ra, Jocelyn and Goodcase, Sam and Silva-Rudberg, Jason A. and Nabulsi, Nabeel B. and Brinkmalm, Ann and Kvartsberg, Hlin and Schöll, Michael and Nilsson, Johanna and Arnsten, Amy F.T. and Huang, Yiyun and Hansson, Oskar and Zetterberg, Henrik and Carson, Richard E. and Blennow, Kaj and van Dyck, Christopher H.}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; biomarkers; CSF; SV2A; synaptic density}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Cerebrospinal fluid and brain positron emission tomography measures of synaptic vesicle glycoprotein 2A : Biomarkers of synaptic density in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.70344}},
  doi          = {{10.1002/alz.70344}},
  volume       = {{21}},
  year         = {{2025}},
}