Abstract Details

Title CSF Levels of NPTX2 are Associated With Decreased Rate of Brain Atrophy Over Time in Cognitively Unimpaired Individuals

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P7 - Poster Session 7 (5:00 PM-6:00 PM)

Poster/Presentation
Number 3-014

Objective Evaluate the association between baseline CSF NPTX2 levels and measures of brain atrophy in participants who were cognitively unimpaired at baseline.

Background Neuronal pentraxin 2 (NPTX2) is a protein involved in synaptic plasticity and regulation of neuronal excitability. Lower baseline cerebrospinal fluid (CSF) NPTX2 levels have been shown to be associated with an earlier onset of symptoms of mild cognitive impairment (MCI), particularly when Alzheimer’s Disease (AD) biomarkers (e.g., cerebrospinal fluid (CSF) levels of amyloid beta (Aβ42/40) and phosphorylated tau (p-tau181) were considered. However, it is not known whether CSF NPTX2 levels among cognitively unimpaired individuals are associated with longitudinal brain atrophy.

Design/Methods Analyses included 213 participants from the prospective longitudinal BIOCARD study, with 13.9 years of MRI follow-up on average. NPTX2 was measured in CSF as a composite of three correlated peptides obtained by quantitative parallel reaction monitoring mass spectrometry. Brain atrophy was measured longitudinally using MRI and quantified in two spatial patterns: (1) a composite of AD-signature regions (SPARE-AD) and (2), a composite of regions sensitive to non-AD related brain aging (SPARE-BA), with higher values indicating more atrophy. Linear mixed effects models assessed the association of baseline NPTX2 levels with rate of change in the MRI atrophy patterns.

Results When covarying AD biomarkers (i.e., CSF p-tau181/(Aβ42/Aβ40 ratio), age, sex, APOE4, and years of education, higher NPTX2 levels were associated with less atrophy over time in both AD-vulnerable regions (SPARE-AD, β=-.008, p=.034) as well as regions sensitive to non-AD brain aging (SPARE-BA, β=-.011 p=.014). These associations did not differ by follow-up diagnosis.

Conclusions Findings suggest NPTX2 slows longitudinal brain atrophy in AD and aging-related regions, after accounting for biomarkers of AD pathology. These findings are consistent with the view that NPTX2 may be a resilience factor in the presence of pathology and modify rates of neurodegeneration.

Authors/Disclosures
Juan P. Vázquez, MD PRESENTER	Dr. Vazquez has nothing to disclose.
Anja Soldan, PhD	Dr. Soldan has nothing to disclose.
Corinne Pettigrew, PhD	Dr. Pettigrew has received research support from NIH/NIA.
Yuxin Zhu, PhD	Dr. Zhu has nothing to disclose.
Claire L. Anderson, MHS	The institution of Miss Anderson has received research support from National Institute on Aging (NIA).
Abhay Moghekar, MD (Johns Hopkins Bayview Medical Center)	Dr. Moghekar has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Deluca and Weizenbaum. Dr. Moghekar has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Silver Golub and Tieteel. The institution of Dr. Moghekar has received research support from NIH. Dr. Moghekar has a non-compensated relationship as a Medical Advisory Board member with Hydrocephalus Association that is relevant to AAN interests or activities. Dr. Moghekar has a non-compensated relationship as a Medical Advisory Board member with Spinal CSF Leak Foundation that is relevant to AAN interests or activities.
Sungtaek Oh (Johns Hopkins University School of Medicine)	Mr. Oh has nothing to disclose.
Chan-Hyun Na, PhD	Dr. Na has nothing to disclose.
Marilyn Albert (Johns Hopkins School of Medicine)	Marilyn Albert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Marilyn Albert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Marilyn Albert has received personal compensation in the range of $500-$4,999 for serving as a Chair with Global Council on Brain Health.
Paul Worley (Johns Hopkins University School of Medicine)	No disclosure on file

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