Comprehensive mapping of synaptic vesicle protein 2A (SV2A) in health and neurodegenerative diseases: a comparative analysis with synaptophysin and ground truth for PET-imaging interpretation.
Humans
Synaptophysin
/ metabolism
Aged
Female
Positron-Emission Tomography
/ methods
Male
Membrane Glycoproteins
/ metabolism
Nerve Tissue Proteins
/ metabolism
Middle Aged
Alzheimer Disease
/ diagnostic imaging
Neurodegenerative Diseases
/ diagnostic imaging
Aged, 80 and over
Frontotemporal Lobar Degeneration
/ diagnostic imaging
Brain
/ diagnostic imaging
Supranuclear Palsy, Progressive
/ diagnostic imaging
Alzheimer’s disease
Frontotemporal lobar degeneration
Postmortem
Progressive supranuclear palsy
SV2A
Synaptophysin
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
15
08
2024
accepted:
09
10
2024
revised:
27
09
2024
medline:
31
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
Synaptic dysfunction and loss are central to neurodegenerative diseases and correlate with cognitive decline. Synaptic Vesicle Protein 2A (SV2A) is a promising PET-imaging target for assessing synaptic density in vivo, but comprehensive mapping in the human brain is needed to validate its biomarker potential. This study used quantitative immunohistochemistry and Western blotting to map SV2A and synaptophysin (SYP) densities across six cortical regions in healthy controls and patients with early-onset Alzheimer's disease (EOAD), late-onset Alzheimer's disease (LOAD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-GRN). We identified region in SV2A density among controls and observed disease- and region-specific reductions, with the most severe in FTLD-GRN (up to 59.5%) and EOAD. EOAD showed a 49% reduction in the middle frontal gyrus (MFG), while LOAD had over 30% declines in the inferior frontal gyrus (IFG) and hippocampus (CA1). In PSP, smaller but significant reductions were noted in the hippocampal formation, with the inferior temporal gyrus (ITG) relatively unaffected. A strong positive correlation between SV2A and SYP densities confirmed SV2A's reliability as a synaptic integrity marker. This study supports the use of SV2A PET imaging for early diagnosis and monitoring of neurodegenerative diseases, providing essential data for interpreting in vivo PET results. Further research should explore SV2A as a therapeutic target and validate these findings in larger, longitudinal studies.
Identifiants
pubmed: 39476256
doi: 10.1007/s00401-024-02816-9
pii: 10.1007/s00401-024-02816-9
doi:
Substances chimiques
Synaptophysin
0
SV2A protein, human
148845-93-6
Membrane Glycoproteins
0
Nerve Tissue Proteins
0
SYP protein, human
0
Types de publication
Journal Article
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
58Subventions
Organisme : NIA NIH HHS
ID : P30AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG062422
Pays : United States
Organisme : NIA NIH HHS
ID : P30AG062422
Pays : United States
Organisme : Alzheimer's Association
ID : AARG-20-678884
Pays : United States
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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