Linear mixed effect models assessed the association of baseline NPTX2 levels with the rate of change in the brain atrophy measures.<h4>Results</h4>When covarying biomarkers of AD pathology (i.e., the ratio of CSF p-tau<sub>181</sub>/(Aβ<sub>1-42</sub>/Aβ<sub>1-40</sub>), age, sex, APOE4 genetic status, and years of education), lower baseline NPTX2 levels were associated with greater atrophy over time in both AD-vulnerable regions (SPARE-AD, standardized estimate = -0.008, p = 0.034) as well as regions sensitive to brain aging (SPARE-BA, standardized estimate = -0.011, p = 0.014). Here, NPTX2 is linked to Alzheimer disease.