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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Elizabeth R Paitel1, Corinne Pettigrew1, Abhay Moghekar1

  • 1Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Higher levels of synaptic proteins neuropentraxin 2 (NPTX2), neurosecretory protein VGF, and glutamate receptor subunit GluA4 in cerebrospinal fluid are linked to better white matter integrity and cognitive function in older adults.

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Cognitive Aging

Background:

  • Synaptic proteins like NPTX2 and VGF in cerebrospinal fluid (CSF) are linked to reduced cognitive decline in older adults.
  • Mechanisms underlying these beneficial effects on cognition remain unclear.
  • This study investigates the relationship between CSF synaptic proteins and white matter microstructure, considering Alzheimer's disease (AD) biomarker levels.

Purpose of the Study:

  • To examine the cross-sectional association between CSF levels of NPTX2, VGF, and GluA4 with MRI-based white matter microstructure.
  • To determine if CSF AD biomarker levels influence the relationship between synaptic proteins and white matter integrity.
  • To explore the connection between synaptic proteins, white matter microstructure, and cognitive performance.

Main Methods:

  • 126 cognitively unimpaired middle-aged and older adults from the BIOCARD study provided CSF and MRI data.
  • Synaptic proteins (NPTX2, VGF, GluA4) were quantified in CSF using mass spectrometry.
  • White matter microstructure (FA, MD) was assessed using diffusion tensor imaging (DTI) in key brain regions.

Main Results:

  • Higher levels of all three synaptic proteins correlated with improved white matter microstructure (higher FA, lower MD) across all assessed regions.
  • These associations remained consistent even after including CSF AD biomarker levels, with no significant interactions found.
  • Enhanced white matter microstructure in cortical and cerebellar tracts was associated with better executive function and visuospatial performance.

Conclusions:

  • Elevated CSF levels of NPTX2, GluA4, and VGF are associated with superior white matter integrity and cognitive performance in older adults.
  • Synaptic proteins may promote cognitive resilience by supporting white matter microstructure.
  • Further longitudinal research is warranted to elucidate the impact of these proteins on white matter and cognition over time.