Transthyretin decrease in plasma of MCI and AD patients: investigation of mechanisms for disease modulation

Area of Science:

• Neuroscience
• Biochemistry
• Gerontology

Background:

• Transthyretin (TTR) is a known potential biomarker in cerebrospinal fluid (CSF) for Alzheimer's disease (AD).
• Limited research exists on TTR levels in the plasma of AD patients.

Purpose of the Study:

• To investigate TTR levels in plasma from patients with mild cognitive impairment (MCI) and AD.
• To explore the potential of plasma TTR as an early biomarker for AD staging and its gender-specific differences.

Main Methods:

• Plasma samples from 55 MCI patients, 56 AD patients, and 41 controls were analyzed for TTR levels.
• Thyroxine binding capacity to TTR and plasma estradiol levels were assessed.
• Genetic analysis for ApoE ε4 allele was performed.

Main Results:

• Plasma TTR levels were significantly decreased in both MCI and AD groups compared to controls.
• Women with MCI and AD exhibited significantly lower plasma TTR levels than men and control women.
• Reduced thyroxine-binding capacity of TTR and lower estradiol levels were observed in MCI and AD women.

Conclusions:

• Plasma TTR is a potential early biomarker for AD, useful for staging the disease.
• The modulation of TTR in AD appears to be gender-dependent, with women showing more pronounced reductions.
• Reduced TTR hormone-binding capacity and estradiol levels may contribute to AD pathogenesis in women.