Abstract Details

Title High Sensitivity Simoa Immunoassays to Evaluate Levels of Postsynaptic density protein 95 and Neuronal Pentraxin II as Predictors of Cognitive Function Loss in Alzheimer’s Diseases

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-004

Background

NPTX2 and PSD95 are post-synaptic proteins involved in synapse plasticity. Their expression in CSF is significantly decreased in neurodegenerative diseases and associated with decline of cognitive functions.

Objective Evaluate the relevance of Neuronal Pentraxin 2 (NPTX2) and Postsynaptic density protein 95 (PSD95) levels in plasma, serum and CSF to assess cognitive decline in Alzheimer’s disease (AD) and other types of dementia.

Design/Methods High sensitivity NPTX2 and PSD95 assays (2 step assay; 35-5 protocol) were developed on the bead-based Simoa HD-X Analyzer. Performances - sensitivity, sample test, specificity, dilution linearity, spike recovery, and stability – were evaluated on Healthy Human (HH) plasma, serum, and CSF (n=20/matrix). Plasma concentrations of AD individuals and age matched HH were compared (n=10 each). Further analysis with other types of dementia is underway.

Results

PSD95 assay LLOD 0.20 pg/mL, LLOQ; 0.58 pg/mL; dilution linearity 102.0 %; spike recovery 100.1 % (in all matrixes). Normal PSD95 ranges: 11.76-199.38 pg/mL in CSF; 4.60-131.50 pg/mL in plasma; 5.03-56.24 pg/mL in serum. We observed a significant increase of PSD95 in plasma of AD samples (AVE 110.1 pg/mL) compared to HH (AVE 28.7 pg/mL); ROC Curve-AUC = 0.810, p = 0.019.

NPTX2 assay LLOD 0.55 pg/mL, LLOQ 3.07 pg/mL dilution linearity 100.5%; spike recovery 99.8 % (in all matrixes). Normal NPTX2 ranges: 411-3729 pg/mL in CSF; 1124-9391 pg/mL in plasma; 1173-11614 pg/mL in serum. The increase of NPTX2 concentration in AD (AVE 2970 pg/mL) vs. HH (AVE 3391 pg/mL) is not significant. However, there is a greater variability in AD (1724-5918 pg/mL) than HH (2061-4110 pg/mL) p = 0.048.

Conclusions

The Simoa NPTX2 and PSD-95 assays can detect and quantify the biomarkers in human CSF, plasma, and serum. Preliminary data show increased PSD95 levels in AD plasma. Additional testing is underway to confirm these results and compare to other neurodegenerative diseases.

Authors/Disclosures
PRESENTER	No disclosure on file
Valerie Brachet, PhD (Fluxus inc.)	Dr. Brachet has received personal compensation for serving as an employee of Quanterix . Dr. Brachet has stock in Quanterix.