Hip Bone Marrow Adiposity as a Risk Factor for Alzheimer's Disease: Insights From Mendelian Randomization Analysis

Area of Science:

• Neuroscience
• Metabolic Research
• Skeletal Biology

Background:

• The bone-brain axis connects skeletal health and neurodegeneration.
• Bone marrow adipose tissue (BMAT) has unique functions but its role in Alzheimer's disease (AD) is unknown.

Purpose of the Study:

• To investigate the causal relationship between six body fat depots and AD risk.
• To determine if bone mineral density (BMD) mediates these associations.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis.
• Employed genome-wide association study (GWAS) summary statistics for six fat depots and AD.
• Conducted mediation analysis to assess the role of femoral neck BMD.

Main Results:

• Total hip BMAT showed a significant causal association with increased AD risk (OR = 1.28).
• Total hip BMAT was inversely associated with femoral neck BMD (β = -0.43).
• No causal link was found between BMD and AD, ruling out bone loss as a mediator.

Conclusions:

• Provides the first genetic evidence linking increased hip BMAT to higher AD risk.
• Supports the role of the bone-brain axis in Alzheimer's disease.
• Identifies hip BMAT as a potential novel therapeutic target for AD.