Biomarkers

Area of Science:

• Neuroscience
• Gerontology
• Biochemistry

Background:

• Dementia is a major global health challenge linked to aging and mortality.
• Multimorbidity, including dementia and frailty, is strongly associated with mortality.
• Fractures and dementia share risk factors like aging and lifestyle, suggesting a connection to bone health.

Purpose of the Study:

• To investigate global changes in bone health markers during Alzheimer's disease (AD) progression.
• To evaluate serum protein levels related to bone metabolism in individuals with AD, Mild Cognitive Impairment (MCI), and healthy controls (HC).

Main Methods:

• Plasma samples from AD (n=95), MCI (n=134), and HC (n=394) participants were analyzed.
• Heparin affinity chromatography enriched plasma proteins, followed by tandem mass spectrometry.
• Proteins were filtered for bone markers and senescence markers.

Main Results:

• Sex-specific alterations in bone-related proteins were observed in MCI and AD.
• In males with MCI, Collagen A1(VI), WNT16, and OLR1 were upregulated; IGFBP-1 and Ephrin-A2 were downregulated.
• In females with MCI, COL was downregulated. In AD, FGF-19 was upregulated and IGFBP-1/COL downregulated.
• Senescence markers WNT16 and HGFm were upregulated in MCI; IL32 was upregulated in AD.

Conclusions:

• Findings indicate sex-dependent changes in bone tissue during neurodegeneration.
• Plasma biomarkers of senescence suggest a link between aging, neurodegeneration, and bone health.
• This research highlights potential new avenues for understanding and managing age-associated diseases.