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Cited by 49Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsGrowth Hormone and Insulin-like Growth Factors

Circulating IGFBP‐2: a novel biomarker for incident dementia

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McGrath, Emer R., Himali, Jayandra J., Levy, Daniel, Conner, Sarah C., DeCarli, Charles S., Pase, Matthew P., Courchesne, Paul, Satizabal, Claudia L. +3 more·2019·Annals of Clinical and Translational Neurology
DOI 10.1002/acn3.50854PMC PMC6764739
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Abstract

Objective: To determine the association between plasma insulin‐like growth factor binding protein 2 (IGFBP‐2) and cognitive outcomes. Methods: We measured plasma IGFBP‐2 levels in 1596 (53% women, mean age 68.7 [SD 5.7] years) dementia‐free Framingham Offspring cohort participants between 1998 and 2001. Multivariable Cox proportional hazards models related plasma IGFBP‐2 to subsequent risk of incident dementia and Alzheimer’s disease. MRI brain measures and cognitive performance were included as secondary outcomes. Results: During a median follow‐up of 11.8 (Q1, Q3: 7.1, 13.3) years, 131 participants developed incident dementia, of whom 98 were diagnosed with Alzheimer’s disease. The highest tertile of IGFBP‐2, compared to the lowest tertile, was associated with an increased risk of incident all‐cause dementia (hazard ratio [HR] 2.89, 95% CI 1.63–5.13) and Alzheimer’s disease (HR 3.63, 95% CI 1.76–7.50) in multivariable analysis. Higher circulating IGFBP2 levels were also cross‐sectionally associated with poorer performance on tests of abstract reasoning but not with MRI‐based outcomes. After adding plasma IGFBP‐2 levels to a conventional dementia prediction model, 32% of individuals with dementia were correctly assigned a higher predicted risk, while 8% of individuals without dementia were correctly assigned a lower predicted risk (overall net reclassification improvement index, 0.40, 95% CI 0.22–0.59). Interpretation: Elevated circulating IGFBP‐2 levels were associated with an increased risk of both all‐cause dementia and Alzheimer’s disease. Addition of IGFBP2 plasma levels to a model of traditional risk factors significantly improved dementia risk classification. Manipulation of insulin‐like growth factor signaling via IGFBP‐2 may be a promising therapeutic target for dementia.

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  • Elevated IGFBP levels have been associated with more severe outcomes in AD patients by inhibiting the neuroprotective effects of IGF proteins.

    “Of note, elevated IGFBP levels have been associated with more severe outcomes in AD patients by inhibiting the neuroprotective effects of IGF proteins50.”

    From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [50]

    The Background (page not provided) says elevated IGF-binding proteins are thought to inhibit the neuroprotective effects of IGFs and reports an association between IGFBP-2 and AD. The Results (page not provided) link elevated IGFBP-2 to the risk of developing AD dementia, not to more severe outcomes among patients who already have AD; the proposed mechanism is also presented as a hypothesis, not an established cause. (LLM, conf=0.84)

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Authors
McGrath, E. R., Himali, J. J., Levy, D., Conner, S. C., DeCarli, C. S., Pase, M. P., Courchesne, P., Satizabal, C. L., Vasan, R. S., Beiser, A. S., & Seshadri, S.
Affiliations
  • Brigham and Women's Hospital (US)
  • Boston University (US)
  • National Institutes of Health (US)
  • University of California, Davis (US)
  • The University of Melbourne (AU)
  • Framingham Heart Study Framingham Massachusetts
Corresponding author
McGrath, Emer R.
ORCID
Venue
Annals of Clinical and Translational Neurology
Publisher
Wiley
Published
2019-08-02
Volume
6
Issue
9
Pages
1659-1670
ISSN
2328-9503 (ISSN-L)
DOI
10.1002/acn3.50854
PMC
PMC6764739
OpenAlex
W2966054655
Cited by
49
References
52
Citations by year
2026: 4 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 1
FWCI
4.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of Clinical and Translational Neurology (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institute on Aging (R01 AG033193, R01 AG049607, R01 AG054076, U01 AG049505, U01 AG052409)
  • National Institute of Neurological Disorders and Stroke (NS017950, UH2 NS100605)
  • National Heart, Lung, and Blood Institute (HHSN268201500001I, N01-HC-25195, R01 HL60040, R01 HL70100)
  • National Heart Foundation of Australia (102052)
  • National Institute of General Medical Sciences (T32GM74905-14)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
IGFBP-2, dementia risk, Alzheimer's disease, biomarkers, plasma biomarkers, cognitive performance, abstract thinking, dementia risk prediction, insulin-like growth factor signaling, Framingham Offspring cohort
MeSH terms
Aged, Alzheimer Disease, Dementia, Female, Humans, Male, Middle Aged, Prospective Studies, Risk, Biomarkers, Incidence, Insulin-Like Growth Factor Binding Protein 3

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