MAR 19, 2014 1:00 PM PDT

ABCA1 and APOE: Intertwined roles in Alzheimers disease

Presented at: Neuroscience
Speaker

Abstract

ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins such as apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE). ABCA1 is essential regulator of high density lipoprotein generation (HDL) a role that defines its significance for cardiovascular disease. ABCA1 and APOE are transcriptionally regulated by Liver X Receptors (LXR) and Retinoic X Receptors (RXR).
The inheritance of 4 allele of APOE is the major genetic risk factor for late-onset Alzheimers disease (AD). Patients carrying APOE4 allele, compared to those with the other two isoforms, have more amyloid plaques a finding replicated in human Amyloid precursor protein (APP) transgenic mice. Recent data suggest that ABCA1 via its control over apoE lipidation may have a role in AD. Studies from our and other groups have demonstrated that lack of ABCA1 increases amyloid deposition and cognitive decline in different AD model mice accompanied by significant decrease in the levels of apoE and apoA-I. In contrast, treatment with LXR or RXR ligands increases ABCA1 and apoE levels and significantly ameliorates amyloid pathology. In a recent study using APP mice we demonstrated that ABCA1 haplo deficiency had a differential effect on the phenotype of APOE3 or APOE4 expressing mice. The lack of one copy of Abca1 significantly aggravated memory deficits, Aβ plaques and Aβ clearance in APP/APOE4 but not in APP/APOE3 mice. Interestingly, we found a correlation between HDL in plasma and amyloid load in brain, suggesting a causative connection between peripheral lipoproteins and Aβ load in the CNS.
In conclusion, these studies demonstrate that future therapies targeting ABCA1 and APOE expression such as LXR/RXR agonists could have a favorable effect on the outcome in AD patients including APO4 carriers.
 


Show Resources
You May Also Like
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
SEP 17, 2021 12:00 PM CST
C.E. CREDITS
SEP 17, 2021 12:00 PM CST
Date: September 16, 2021 Time: 9:00pm (PDT), 12:00am (EDT) 3D cellular models like organoids and spheroids offer an opportunity to better understand complex biology in a physiologically rele...
OCT 20, 2021 10:00 AM PDT
C.E. CREDITS
OCT 20, 2021 10:00 AM PDT
Date: October 20, 2021 Time:10:00am (PDT), 1:00pm (EDT) As the prevalence of Diabetes continues to rise in many areas across the globe, healthcare providers continue to look for methods that...
NOV 30, 2021 10:00 AM PST
C.E. CREDITS
NOV 30, 2021 10:00 AM PST
Date: November 30, 2021 Time: 10:00am (PDT), 1:00pm (EDT) The prevalence of thyroid disease worldwide has served as a catalyst for healthcare providers to study various tools and methods to...
NOV 09, 2021 11:00 AM PST
C.E. CREDITS
NOV 09, 2021 11:00 AM PST
Date: November 09, 2021 Time: 11:00am (PDT), 02:00pm (EDT) Clinical translation of human pluripotent stem cells (hPSCs) requires advanced strategies that ensure safe and robust long-term gro...
JAN 13, 2022 9:00 AM PST
C.E. CREDITS
JAN 13, 2022 9:00 AM PST
Date: January 13, 2022 Time: 09:00am (PST), 12:00pm (EST) Recently, the Infectious Disease Society of America released guidance on how to approach treatment of infections caused by multidrug...
MAR 19, 2014 1:00 PM PDT

ABCA1 and APOE: Intertwined roles in Alzheimers disease

Presented at: Neuroscience


Show Resources
Loading Comments...
Show Resources