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
Year: 2026
Type: article
Study design: Observational Study
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.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71097
Institutions: Hôpital de l'Enfant-Jésus, Centre de recherche du CHU de Québec-Université Laval, CHU de Québec-Université Laval, Université Laval, Institut universitaire de cardiologie et de pneumologie de Québec, Institut Universitaire de Gériatrie de Montréal, University of Wisconsin–Madison, Sahlgrenska University Hospital, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Gothenburg
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Funders: Pfizer, Réseau québécois de recherche sur le vieillissement, Ministère de la Santé et des Services sociaux, Consortium canadien en neurodégénérescence associée au vieillissement, European Commission, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Courtois Foundation, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, Fonds de Recherche du Québec - Santé
Awards: G1110051197, G1343867371, G1802301745, Phase Two of the Canadian Consortium on Neurodegeneration in Aging, G2587393393, G2968927823, FGF-21 in Alzheimer's disease., Fluid biomarkers for neurodegenerative dementias, G3914690605, G4260843567, G5040492720, Fluid biomarkers for neurodegenerative dementias, CASCADE: CAuSe or Consequence in Alzheimer DiseasE?, G6158734006, G6361952146, G712881263, G7236548507, G7972240148, Risk factors and markers for early detection of Alzheimer's Disease: focus on early-life stress, inflammation and lipid mediators
OpenAlex ID: W7127316674