NPTX2 marker for cognitive impairment


In a new study the authors examined whether cerebrospinal fluid (CSF) baseline levels of the synaptic protein NPTX2 predict time to onset of symptoms of Mild Cognitive Impairment (MCI), both alone and when accounting for traditional CSF Alzheimer's disease (AD) biomarker levels.

In Cox regression models, lower baseline NPTX2 levels were associated with an earlier time to MCI symptom onset (HR=0.76, SE=0.09, p=0.023). This association was significant for progression within 7 years (p=0.036) and after 7 years from baseline (p=0.001). Baseline NPTX2 levels improved prediction of time to MCI symptom onset after accounting for baseline AD biomarker levels (p<0.01), and NPTX2 did not interact with the CSF AD biomarkers or APOE-ε4 genetic status. In linear mixed effects models, higher baseline p-tau181 and t-tau levels were associated with higher baseline levels of NPTX2 (both p<0.001) and greater rates of NPTX2 declines over time.

In conclusion, NPTX2 may be a valuable prognostic biomarker during preclinical AD that provides additive and independent prediction of MCI onset among individuals who are cognitively normal. We hypothesize that NPTX2-mediated circuit homeostasis confers resilience during the early phase of AD.

Source: Annals of Neurology