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

**Authors:** Manuela Dicarlo, Patrizia Pignataro, Daniele Urso, Chiara Zecca, Maria Teresa Dell'Abate, Francesco Borlizzi, Valentina Gnoni, Alessia Giugno, Angela Oranger, Graziana Colaianni, Roberta Zerlotin, Clelia Suriano, Silvia Colucci, Giancarlo Logroscino, Maria Grano

PMC · DOI: 10.1002/dad2.70297 · 2026-03-11

## TL;DR

This study found that higher levels of sclerostin in cerebrospinal fluid are linked to early Alzheimer's disease and could serve as a potential biomarker.

## Contribution

The study identifies sclerostin as a potential biomarker for early Alzheimer's disease stages by analyzing its correlation with AD biomarkers.

## Key findings

- CSF sclerostin levels increased in patients with Alzheimer's disease.
- Sclerostin correlated negatively with amyloid beta 42 and positively with phosphorylated tau and dementia severity.
- Sclerostin shows potential as a biomarker in early Alzheimer's disease.

## Abstract

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.

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.

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.

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.

We studied sclerostin levels in patients with Alzheimer's disease (AD) who had been biologically classified.Cerebrospinal fluid (CSF) sclerostin was increased in patients with AD.CSF sclerostin correlated with amyloid beta, phosphorylated tau, total tau, and dementia severity.Sclerostin could be a biomarker in the early phase of AD.

We studied sclerostin levels in patients with Alzheimer's disease (AD) who had been biologically classified.

Cerebrospinal fluid (CSF) sclerostin was increased in patients with AD.

CSF sclerostin correlated with amyloid beta, phosphorylated tau, total tau, and dementia severity.

Sclerostin could be a biomarker in the early phase of AD.

## Linked entities

- **Diseases:** Alzheimer's disease (MONDO:0004975), dementia (MONDO:0001627)

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, SOST (sclerostin) [NCBI Gene 50964] {aka CDD, DAND6, SOST1, VBCH}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** dementia (MESH:D003704), amyloid (MESH:C000718787), cognitive impairment (MESH:D003072), memory impairment (MESH:D008569), neurodegeneration (MESH:D019636), AD (MESH:D000544)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12976974/full.md

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Source: https://tomesphere.com/paper/PMC12976974