Possible Clues to Alzheimer’s Disease
(Ivanhoe Newswire) ““ The little-studied amyloid peptide may be promoting Alzheimer’s disease (AD), according to this study. Their findings show that the peptide is more abundant, more neurotoxic, and exhibits a higher propensity to aggregate than other agents studied earlier.
An irreversible, progressive brain disease affecting millions worldwide, Alzheimer’s disease is devastating for its victims, robbing them of their memory and cognitive skills and ultimately of their lives. Even after decades of research, however, the causes of AD remain elusive. Two features in the brain, abnormal clumps (senile plaques) and tangled bundles of fibers (neurofibrillary tangles), are known to characterize AD, but there is little consensus on the link between these features and the underlying roots of the disease.
One hypothesis that has attracted widespread support proposes that AD is caused by the buildup of the senile plaques, and in particular of their main constituent, amyloid-ÃƒÅ¸ peptides (AÃƒÅ¸). Two major forms of AÃƒÅ¸, AÃƒÅ¸40 and AÃƒÅ¸42, have been associated with genetic mutations causing early-onset AD, and have thus received considerable research attention. The role of longer AÃƒÅ¸ species, in contrast, which also exist in the brains of Alzheimer’s patients, has not yet been fully investigated.
In their current work, the researchers focused on AÃƒÅ¸43, an amyloid-ÃƒÅ¸ peptide found just as often in patient brains as AÃƒÅ¸42, but about which relatively little is known. To study the peptide’s role in AD, they generated mice with a mutation causing overproduction of AÃƒÅ¸43, and used a highly sensitive system to distinguish between concentrations of AÃƒÅ¸40, AÃƒÅ¸42 and AÃƒÅ¸43.
Their surprising results reveal that AÃƒÅ¸43 is even more abundant in the brains of AD patients than AÃƒÅ¸40, and more neurotoxic than AÃƒÅ¸42. AÃƒÅ¸43 also exhibits the highest propensity to aggregate and considerably accelerates amyloid pathology. Moreover, unlike the other two AÃƒÅ¸ species, which exist in human and mouse brains at birth, AÃƒÅ¸43 levels appear to increase with age, consistent with the pattern of AD onset.
The findings reveal the possible value of AÃƒÅ¸43 as a biomarker for diagnosis of AD and suggest a potential role in new approaches for preventing AD-causing amyloidosis, promising hope to AD sufferers around the world.
SOURCE: Nature Neuroscience, published online July 3, 2011