CSF Levels of NPTX2 Are Associated With Less Brain Atrophy Over Time in Cognitively Unimpaired Individuals

Area of Science:

• Neuroscience
• Biomarker Research
• Aging Studies

Background:

• Neuronal Pentraxin 2 (NPTX2) is a synaptic protein influencing neuronal function.
• Lower baseline CSF NPTX2 levels correlate with earlier mild cognitive impairment (MCI) onset.
• The association between CSF NPTX2 and longitudinal brain atrophy in unimpaired individuals is unknown.

Purpose of the Study:

• To investigate the relationship between baseline CSF NPTX2 levels and long-term brain atrophy.
• To assess if NPTX2 levels predict atrophy rates in cognitively unimpaired individuals.

Main Methods:

• Analysis of 213 cognitively unimpaired participants from the BIOCARD study with long-term MRI follow-up (average 13.9 years).
• CSF NPTX2 measured using quantitative parallel reaction monitoring mass spectrometry.
• Longitudinal brain atrophy assessed using spatial patterns of AD-signature regions (SPARE-AD), aging-sensitive regions (SPARE-BA), and medial temporal lobe (MTL) volumes.
• Linear mixed-effect models used to evaluate associations between NPTX2 and atrophy rates.

Main Results:

• Lower baseline CSF NPTX2 levels were significantly associated with greater atrophy over time in both AD-vulnerable regions (SPARE-AD) and aging-sensitive regions (SPARE-BA).
• These associations remained significant after adjusting for Alzheimer's Disease (AD) biomarkers (p-tau181/Aβ ratio), age, sex, APOE4 status, and education.
• The findings were independent of subsequent MCI or dementia diagnoses.

Conclusions:

• CSF NPTX2 levels are associated with slower longitudinal brain atrophy in regions vulnerable to AD and aging.
• NPTX2 may function as a resilience factor, potentially modifying neurodegeneration rates.
• These results highlight NPTX2's role in brain aging and neurodegenerative processes.