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.

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    • Source:
      Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0412041 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-0533 (Electronic) Linking ISSN: 00016322 NLM ISO Abbreviation: Acta Neuropathol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin : Springer Verlag
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    • Abstract:
      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.
      (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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    • Grant Information:
      P30AG062422 United States AG NIA NIH HHS; P30AG062422 United States AG NIA NIH HHS; P30AG062422 United States AG NIA NIH HHS; P30AG062422 United States AG NIA NIH HHS; AARG-20-678884 United States ALZ Alzheimer's Association
    • Contributed Indexing:
      Keywords: Alzheimer’s disease; Frontotemporal lobar degeneration; Postmortem; Progressive supranuclear palsy; SV2A; Synaptophysin
    • Accession Number:
      0 (Synaptophysin)
      148845-93-6 (SV2A protein, human)
      0 (Membrane Glycoproteins)
      0 (Nerve Tissue Proteins)
      0 (SYP protein, human)
    • Publication Date:
      Date Created: 20241030 Date Completed: 20241030 Latest Revision: 20241105
    • Publication Date:
      20241106
    • Accession Number:
      10.1007/s00401-024-02816-9
    • Accession Number:
      39476256