Cerebrospinal fluid sclerostin levels in the early Alzheimer's disease stages.

INTRODUCTION: Sclerostin, a negative regulator of bone formation, has been involved in memory impairment in Alzheimer's disease (AD) mouse models and is increased in elderly people at risk of AD. Here, we investigated sclerostin's role across the clinical stages of AD. METHODS: We evaluated cerebrospinal fluid (CSF) sclerostin levels in patients with dementia due to AD, mild cognitive impairment, and subjective memory complaints, biologically characterized via the amyloid/tau/neurodegeneration classification. Results were correlated with AD biomarkers, amyloid beta (Aβ) 42, phosphorylated tau (p-tau), and total tau (t-tau), and clinical parameters of dementia severity. RESULTS: CSF sclerostin increased in patients with dementia due to AD and correlated negatively with Aβ42 and positively with p-tau, t-tau, and dementia severity. DISCUSSION: The association of CSF sclerostin with Aβ42, tau pathology, and dementia severity in the early disease stages is of great clinical relevance for the identification of sclerostin as a promising biomarker in early AD stages.