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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
Published on: January 28, 2014
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Biomarkers
Hamilton Se-Hwee Oh1,2, Deniz Yagmur Urey3, Linda Karlsson4
1Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
Summary
New Alzheimer's disease (AD) biomarkers, YWHAG:NPTX2 synapse protein ratio in CSF and a plasma signature, show promise for predicting cognitive decline. These findings highlight synapse dysfunction as a key factor in AD progression.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Proteomics
Background:
- Alzheimer's disease (AD) exhibits significant heterogeneity in cognitive decline rates.
- Current biomarkers (amyloid-beta and tau) explain limited variance in AD-related cognitive impairment (CI).
Purpose of the Study:
- To identify novel cerebrospinal fluid (CSF) biomarkers for CI in AD.
- To investigate the prognostic value of synapse proteins in AD.
- To develop a plasma-based biomarker signature for AD progression.
Main Methods:
- Cerebrospinal fluid (CSF) proteomics on 3,397 individuals across six cohorts.
- Machine learning to derive the CSF YWHAG:NPTX2 synapse protein ratio.
- Evaluation of a plasma proteomic signature in 13,401 samples.
Main Results:
- CSF YWHAG:NPTX2 ratio strongly correlates with CI, independent of Aβ and tau.
- This ratio improves prediction of cognitive decline beyond established biomarkers.
- The YWHAG:NPTX2 ratio increases with normal aging and faster in APOE4 carriers.
- Defined thresholds stratify individuals by future cognitive resilience or decline.
- A plasma signature partially recapitulates CSF YWHAG:NPTX2 findings.
Conclusions:
- CSF YWHAG:NPTX2 and plasma signature are robust prognostic biomarkers for AD.
- These biomarkers offer value beyond current gold-standard AD markers.
- Synapse dysfunction is implicated as a central mechanism in AD dementia.
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