Elevated sclerostin levels in cerebrospinal fluid are associated with cognitive impairment in the Alzheimer's disease continuum

Introduction Bone-derived sclerostin impairs cognitive function in both patients with Alzheimer's disease (AD) and mouse models of AD. For the first time, we explored the correlation of sclerostin with neurocognitive domains in the AD continuum. Methods Sclerostin levels were measured in the cerebrospinal fluid (CSF) of a cohort of individuals with biological evidence of AD pathology, including patients with AD dementia, mild cognitive impairment due to AD (MCI), and subjective memory complaints (SMC). Correlations were examined between sclerostin and domain-specific cognitive scores. Results CSF sclerostin correlated with overall cognitive function, as well as with all cognitive domains impaired in AD. Of note, MCI patients with high CSF sclerostin levels displayed a worse overall and domain-specific neurocognitive performance. Discussion Our results evidenced the negative impact of sclerostin on all the cognitive domains predominantly in prodromal AD, suggesting its potential role as a biomarker of cognitive decline in the early stages of the disease.