No 15/September 7, 2005
Molecule protects against developing Alzheimers Disease
A molecule expressed by nerve cells may protect humans from
developing Alzheimer’s Disease (AD). In particular, it may reduce the risk of
the formation of senile plaques in the brains of patients with AD, as
researchers from the
A hallmark of Alzheimer disease are protein plaques in the brain which accumulate over many years. They are derived from the amyloid precursor protein (APP) which for unknown reasons is chopped up into smaller fragments, including the amyloid beta peptide, which forms these dangerous plaques. The plaques destroy the patients’ nerve cells and lead to dementia, impairing the patients memory, thinking, and behaviour. According to the National Institutes of Health (NIH) more than four million Americans suffer from AD, an incurable disease. The older one gets, the greater the risk of developing this disease. It is estimated that about half of the individuals over 85 years of age are affected.
Professor Willnow and his colleagues were able to demonstrate that the molecule, named sorLa (abb. sorting protein-related receptor), binds to APP in nerve cells and thus prevents its dissection into the amyloid beta peptide. They could also show that genetically modified mice which cannot produce sorLA have increased levels of amyloid beta peptides because APP is destructed at a much higher rate than in healthy animals.
The researchers also looked at the brains of patients who died from AD and compared them with subjects who had not suffered from this disease. Surprisingly, the nerve cells of the AD patients had not produced sorLA, but the nerve cells of the control group had done so. The researchers conclude that in individuals whose brains produce little or no sorLA, the uncontrolled production of amyloid beta peptides likely accelerates onset and progression of neurodegenerative processes, making sorLA an important risk factor for AD.
Ongoing research is directed towards identification of substances that could increase the production of sorLA in the brain of those people that produce insufficient amounts of the molecule. The researchers hope that in the future it will be possible to pharmacologically reduce the formation of these dangerous plaques in the brain by modulating sorLA levels.
*Neuronal
sorting protein-rtelated receptor sorLA/LR11 regulates processingof the amyloid
precursor protein Olav M. Andersen*, Juliane Reiche*,
Vanessa Schmidt*, Michael Gotthardt*, Robert Spoelgen*,
Joachim Behlke*, Christine A. F. von Arnim†, Tilman
Breiderhoff*, Pernille Jansen‡, Xin Wu$, Kelly
R. Bales§, Roberto Cappai¶, Colin L. Masters¶,
Jørgen Gliemann‡, Elliot J. Mufson║, Bradley T.
Hyman†, Steven M. Paul§, Anders Nykjær‡, and
Thomas Willnow*,** *Max
Delbrueck Center for Molecular Medicine, 13125 Berlin-Buch, Germany; †Massachusetts
General Hospital, Charlestown, MA 02129; §Lilly Research
Laboratories, Indianapolis, IN •••; ║Department of
Neurological Sciences, Rush University Medical Center, Chicago, IL •••; ‡Institute
of Medical Biochemistry, University of Aarhus, DK-800, Denmark; and ¶Mental
Health Research Institute of Victoria, Parkville •••, Australia
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