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Related Experiment Video

Updated: Jan 7, 2026

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

Claire L Anderson1, Alden L Gross2,3, Corinne Pettigrew1

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

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Higher levels of synaptic proteins neuronal pentraxin 2 (NPTX2) and VGF may protect against cognitive decline, even with Alzheimer's disease (AD) pathology. These findings suggest potential therapeutic targets for AD and related neurodegenerative diseases.

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Neurodegenerative Diseases

Background:

  • Synaptic proteins like neuronal pentraxin 2 (NPTX2) and VGF may offer resilience against Alzheimer's disease (AD) and other neurodegenerative conditions.
  • Understanding these synaptic proteins during preclinical AD is crucial for early intervention.

Purpose of the Study:

  • To investigate the association between baseline cerebrospinal fluid (CSF) levels of VGF, NPTX2, and GluA4 with long-term cognitive trajectories in cognitively unimpaired individuals.
  • To determine if these synaptic proteins predict cognitive decline independent of AD pathology biomarkers.

Main Methods:

  • CSF levels of NPTX2, GluA4, and VGF were measured using mass spectrometry in 269 cognitively unimpaired participants.
  • Alzheimer's disease biomarkers (Ab1-42/Ab1-40, p-tau181) were quantified using Lumipulse G1200 assays.
  • Linear mixed effects models analyzed associations between synaptic proteins and cognitive performance over a mean follow-up of 15.9 years.

Main Results:

  • Higher baseline levels of NPTX2 and VGF were associated with slower rates of decline in global cognition and episodic memory, even after accounting for AD biomarker levels.
  • VGF was also linked to reduced executive function decline, with a similar trend observed for NPTX2.
  • No significant association was found between GluA4 levels and cognitive change.

Conclusions:

  • Baseline NPTX2 and VGF levels are linked to preserved cognitive function, suggesting a protective role against cognitive decline in the presence of AD pathology.
  • These synaptic proteins may represent potential therapeutic targets for mitigating cognitive decline in AD.
  • The findings support the hypothesis of synaptic resilience mechanisms in neurodegenerative diseases.