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Decrease of transthyretin synthesis at the blood-cerebrospinal fluid barrier of old sheep
Ruo L Chen1, Senarath B P Athauda, Nouhad A Kassem
1Institute of Gerontology, Franklin-Wilkins Building, King's College, 150 Stamford Street, London SE1 9NH. ronnie.chen@kcl.ac.uk
Summary
Aging reduces transthyretin (TTR) synthesis in the choroid plexus (CP), impacting cerebrospinal fluid (CSF) thyroxine (T4) transport and beta-amyloid clearance, potentially increasing Alzheimer's disease risk.
Area of Science:
- Neuroscience
- Biochemistry
- Aging Research
Background:
- Transthyretin (TTR) is crucial for thyroxine (T4) transport and beta-amyloid peptide chelation in cerebrospinal fluid (CSF).
- The choroid plexus (CP) synthesizes and secretes TTR into the CSF.
- Age-related changes in TTR function may impact neurological health and Alzheimer's disease (AD) risk.
Purpose of the Study:
- To investigate age-related alterations in TTR synthesis and function within the sheep choroid plexus (CP).
- To assess the impact of aging on TTR's role in T4 homeostasis and beta-amyloid clearance in CSF.
Main Methods:
- Collected CSF and CPs from young and old sheep.
- Assessed de novo protein synthesis using 14C-leucine perfusion.
- Evaluated T4 transport using 125I-T4 perfusion and measured TTR mRNA levels.
Main Results:
- Old sheep exhibited lower CSF TTR levels compared to young sheep.
- CP protein synthesis, including TTR, was reduced in old sheep.
- Reduced T4 transport capacity (Vmax and Kd) was observed in old sheep CP.
Conclusions:
- Aging impairs CP's capacity for TTR synthesis and T4 transport, potentially compromising CSF T4 homeostasis.
- Reduced TTR function with age may diminish beta-amyloid clearance, posing an increased risk for Alzheimer's disease.