Biomarkers of ABCA-1 Functions in Alzheimer’s Disease
- Carrying the ApoE ε4 allele is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD)
- Using a novel approach, we examined the capacity of cerebrospinal fluid (CSF) to transport cholesterol from cells expressing the ABCA1 transporter.
- We demonstrated significantly reduced ABCA1 mediated cholesterol efflux capacity in participants with mild cognitive impairment and AD compared to healthy controls. (ABCA1‐Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer’s Disease).
- We then found that ApoE4 decreases ABCA1 mediated cholesterol efflux promotes by trapping ABCA1 in endosomes (https://www.jneurosci.org/content/39/48/9611).
- We hypothesize that this functional capacity of CSF can serve as a biomarker providing unique information regarding pathophysiology of AD and identifying participants that could be benefit from ABCA1 agonist treatments.
- In this project, we propose that ABCA1 mediated cholesterol efflux capacity and HDL particle numbers in CSF are novel and informative AD biomarkers to guide future therapies
- Project Funding: Biomarkers of ABCA-1 Functions in Alzheimer’s Disease.