The potential value of NPTX2 as a biomarker is further advanced by the observation that NPTX2 appears ‘orthogonal’ to Aß and tau since NPTX2 is not reduced as a direct consequence of Aß amyloid in mouse models, appears independent of Aß in human asymptomatic AD (pre AD), and reductions of CSF NPTX2 do not correlate with reduction of CSF Aß42 or increases of tau/p-tau. The gene discussed is NPTX2; the disease is Alzheimer disease.