Navigation Links
Mechanism explains link between apolipoprotein E and Alzheimer's disease
Date:6/11/2008

Scientists have discovered a previously unknown mechanism by which apolipoprotein E, a molecule whose mutation is linked to Alzheimer's disease (AD), stimulates degradation of sticky amyloid beta (A?) protein within the brain. The research, published by Cell Press in the June 12 issue of the journal Neuron, may lead to a powerful new therapy for this devastating disease.

One of the primary characteristics of AD is the accumulation and deposition of neuron-damaging clumps of A? protein. Apolipoprotein E (ApoE), a cholesterol transport protein, is known to be a key regulator of brain A? levels, and it is likely that processes that regulate ApoE activity will influence A? deposition and clearance. "An isoform of ApoE, ApoE4, has been shown to confer dramatically increased risk for late-onset AD; however, the basis for this remains one of the major unanswered questions of disease pathogenesis," writes study author Dr. Gary E. Landreth from the Alzheimer Research Laboratory at Case Western Reserve University School of Medicine in Cleveland, Ohio.

Dr. Landreth and colleagues sought to unravel the link between ApoE, A? clearance in the brain, and an enhanced risk for AD. The researchers found that ApoE profoundly enhanced the intracellular and extracellular degradation of A?. This enhancement varied for different isoforms of ApoE with the ApoE4 isoform exhibiting an impaired ability to promote A? degradation when compared to other ApoE isoforms. The number of lipid molecules associated with ApoE was also critical to its ability to stimulate A? degradation. Activation of liver X receptors (LXRs) to enhance expression of lipidated ApoE significantly facilitated A? degradation. Importantly, use of an LXR agonist to increase lipidated forms of ApoE in a mouse model of AD resulted in reduced A? plaque levels and an improvement in contextual memory.

The results of this study document a major role for ApoE in the stimulation of A? degradation within the brain and highlight the importance of lipidation to the function of ApoE. This work also explains the previous observation that inactivation of a gene which helps the brain to process lipids (called Abca1) resulted in decreased levels of ApoE along with a seemingly paradoxical elevation of A? levels and plaque formation in mice. "Our data suggest that therapeutic agents that increase the levels of lipidated forms of ApoE, including LXR agonists, represent a potentially efficacious therapy for AD," concludes Dr. Landreth.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related biology news :

1. Jefferson receives $11.6M NIH grant to study novel mechanisms of heart failure
2. Fruit fly avoidance mechanism could lead to new ways to control pain in humans
3. Researchers uncover mechanism of action of antibiotic able to reduce neuronal cell death in brain
4. Scientists clarify a mechanism of epigenetic inheritance
5. CSHL scientists identify a mechanism that helps fruit flies lock-in memories
6. A common genetic mechanism discovered in nitrogen-fixing plants
7. Mechanisms of plant-fungi symbiosis characterized by DOE Joint Genome Institute
8. Scientists uncover a novel mechanism that regulates carbon dioxide fixation in plants
9. The Uukuniemi virus helps to explain the infection mechanism of bunyaviruses
10. USC researchers identify mechanism that controls activation of stem cells during hair regeneration
11. New treatment mechanisms for schizophrenia
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/18/2016)... , Jan. 18, 2016  Extenua Inc., ... that simplifies the use and access of ubiquitous ... go-to-market partnership with American Cyber.  ... extensive experience leading transformational C4ISR and Cyber initiatives ... integrating the latest proven technology solutions," said ...
(Date:1/13/2016)... , January 13, 2016 /PRNewswire/ ... announced the addition of the  "India ... Estimation & Forecast (2015-2020)"  report ... http://www.researchandmarkets.com/research/7h6hnn/india_biometrics ) has announced the addition ... Identification Market - Estimation & Forecast ...
(Date:1/8/2016)... and MANCHESTER, United Kingdom , Jan. 8, ... of innovative sensor-based diagnostic products, today announced the closing of ... and existing investors.  Proceeds from the financing will be used ... a hand-held device for detecting early-stage pressure ulcers. ... after receiving CE Mark approval. The device,s introduction ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... ... February 04, 2016 , ... Franz Inc. , an ... technology has been recognized As “ Best in Semantic Web Technology - USA ... Corporate America, it’s our priority to showcase prominent professionals who are excelling in ...
(Date:2/3/2016)... , Feb. 3, 2016  With the ... patent cliff that is underway, therapies such as ... for a whole host of indications are in ... aid in the development and production of these ... poor quality and high costs, novel approaches and ...
(Date:2/3/2016)... ... February 03, 2016 , ... ProMIS Neurosciences is currently in ... to misfolded, propagating strains of Amyloid beta involved in Alzheimer’s disease. The Company ... , Following on from the first misfolded Amyloid beta target announced on Nov. ...
(Date:2/3/2016)... , ... February 03, 2016 , ... ... to aid in the rapid development and ongoing quality control of molecular assays ... outbreak is extremely high,” Dr. Gregory R. Chiklis, President and CEO of ZeptoMetrix, ...
Breaking Biology Technology: