A possible explanation for the discrepancy between brain and CSF expression may be that only a fraction of the increased SMOC1 produced in AD binds to Aβ in plaques, while the remaining pool of soluble SMOC1 that does not complex with fibrillar Aβ is continuously cleared from the brain, thus accounting for the increased levels of SMOC1 in the CSF and plasma. Here, SMOC1 is linked to Alzheimer disease.