Overlooked Amyloid Beta Peptide May Promote Alzheimer’s Disease

A largely overlooked amyloid peptide, Aβ43, promotes Alzheimer’s disease to a greater extent than many well-studied amyloidogenic agents, says a new study.

AsianScientist (Jul. 4, 2011) – Researchers at the RIKEN Brain Science Institute (BSI) in Japan, together with their collaborators, have found that a largely overlooked amyloid peptide, Aβ43, promotes Alzheimer’s disease (AD) to a greater extent than many well-studied amyloidogenic agents.

Alzheimer’s disease is a degenerative, terminal brain disease that affects millions worldwide and is predicted to affect 1 in 85 people globally by 2050. It is a disease that progressively robs its victims of memory and cognitive skills, ultimately leading to loss of bodily functions and the victim’s life.

Abnormal clumps (senile plaques) and tangled bundles of fibers (neurofibrillary tangles) in the brain are known to characterize AD, although the link between these characteristics and the underlying roots of the disease have yet to be discovered.

One hypothesis that has gained widespread support is that AD is caused by the buildup of senile plaques. In particular, research has focused on amyloid-β peptides (Aβ) which are the main constituents of senile plaques. Considerable research has thus been carried out on the two major forms of Aβ, Aβ40 and Aβ42, which have been associated with genetic mutations that cause early-onset AD.

In contrast, the RIKEN researchers focused their investigations on the less-studied Aβ43 peptide which is also found in the brains of AD patients.

To study the role of Aβ43, the researchers introduced a genetic mutation that caused overproduction of Aβ43 in mice. They also established a highly sensitive assay that could measure and distinguish between Aβ40, Aβ42 and Aβ43 concentrations.

Their surprising results, published online today in Nature Neuroscience, revealed that Aβ43 may in fact be more abundant in the brains of AD patients than Aβ40, and more neurotoxic than Aβ42. Aβ43 also exhibits the highest propensity to aggregate and considerably accelerates amyloid pathology. Moreover, unlike the other two Aβ species, which are present in human and mouse brains at birth, Aβ43 levels appear to increase with age, consistent with the pattern of AD onset.

These findings raise the possibility that Aβ43 can be used as a biomarker for diagnosing AD and in developing new approaches for preventing AD-causing amyloidosis, paving the way towards easing the suffering of AD patients around the globe.

The article can be found at: Saito et al. (2011) Potent Amyloidogenicity And Pathogenicity Of Aβ43.

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Source: RIKEN.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Wendy Yang is a public health sciences major at the University of California, Irvine. She enjoys covering science and research news from Asia.

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