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Alzheimer's & dementia : the journal of the Alzheimer's Association
Published

Distinct alterations of adiponectin, fibroblast growth factor 21 (FGF-21), and insulin-like growth factor binding protein 2 (IGFBP-2) link dysmetabolism with cognitive decline across the Alzheimer's disease spectrum

Authors

Caroline Dallaire-Théroux, Helena L Denis, Rosalie Cottez, Cyntia Tremblay, Amélie Provencher, Josue Valentin-Escalera, Manon Leclerc, Andreanne Loiselle, Marine Tournissac, Olivier Potvin, Sylvie Belleville, Anne Gangloff, Frederic Picard, Henrik Zetterberg, Consortium for the Early Identification of Alzheimer's Disease – Quebec (CIMA‐Q), Frédéric Calon

Abstract

Alzheimers Dement. 2026 Feb;22(2):e71097. doi: 10.1002/alz.71097.

ABSTRACT

INTRODUCTION: Metabolic disorders are risk factors for Alzheimer's disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers - adiponectin, fibroblast growth factor 21 (FGF-21), and insulin-like growth factor binding protein 2 (IGFBP-2) - and AD.

METHODS: Participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and cognitively healthy (CH) controls were from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort (n = 287). Serum adiponectin, FGF-21, and IGFBP-2 concentrations were measured, compared between groups, and assessed for associations with clinical, cognitive, biochemical, and magnetic resonance imaging (MRI) data.

RESULTS: Metabolic dysfunction was linked to lower adiponectin and IGFBP-2, but higher FGF-21. Both FGF-21 and IGFBP-2 increased with age and were inversely associated with cognitive performance. IGFBP-2 was elevated at SCD stage and correlated with plasma tau phosphorylated at threonine 181 and amygdala atrophy. Adiponectin was unrelated to cognition.

DISCUSSION: These findings suggest that IGFBP-2 and, to a lesser extent, FGF-21 may serve as early biomarkers of cognitive impairment, reflecting intricate links between peripheral dysmetabolism and AD.

PMID:41630588 | DOI:10.1002/alz.71097

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg