Circulating IGFBP-2: a novel biomarker for incident dementia

Area of Science:

• Neuroscience
• Biochemistry
• Gerontology

Background:

• Cognitive decline and dementia are significant public health concerns.
• Insulin-like growth factor binding protein 2 (IGFBP-2) plays a role in various biological processes, including brain development and function.
• The association between IGFBP-2 and dementia risk is not fully understood.

Purpose of the Study:

• To investigate the relationship between plasma levels of IGFBP-2 and the risk of developing dementia and Alzheimer's disease.
• To assess the utility of IGFBP-2 in improving dementia risk prediction models.
• To explore the association of IGFBP-2 with cognitive performance and brain imaging outcomes.

Main Methods:

• Plasma IGFBP-2 levels were measured in 1596 dementia-free participants from the Framingham Offspring cohort.
• Multivariable Cox proportional hazards models were used to assess the risk of incident dementia and Alzheimer's disease over a median follow-up of 11.8 years.
• Cognitive tests and MRI brain measures were included as secondary outcomes.

Main Results:

• The highest tertile of IGFBP-2 was associated with a significantly increased risk of all-cause dementia (HR 2.89) and Alzheimer's disease (HR 3.63).
• Higher IGFBP-2 levels correlated with poorer abstract reasoning but not with MRI outcomes.
• Adding plasma IGFBP-2 to conventional risk factors improved dementia risk classification by 40% (net reclassification improvement index).

Conclusions:

• Elevated circulating IGFBP-2 levels are a significant risk factor for dementia and Alzheimer's disease.
• Plasma IGFBP-2 levels can enhance the accuracy of dementia risk prediction.
• Targeting insulin-like growth factor signaling via IGFBP-2 presents a potential therapeutic avenue for dementia prevention and treatment.