A largely overlooked amyloid-β (Aβ) peptide could play a greater role in the pathogenesis of Alzheimer disease (AD) than previously envisaged, scientists claim. Mice engineered to overexpress Aβ43 were found to display impairment
A largely overlooked amyloid-β (Aβ) peptide could play a greater role in the pathogenesis of Alzheimer disease (AD) than previously envisaged, scientists claim. Mice engineered to overexpress Aβ43 were found to display impairment of short-term memory and acceleration of amyloid-β pathology. This was accompanied by pronounced accumulation of Aβ43 in plaque cores that were similar in biochemical composition to those observed in the brains of affected human patients.
In fact, the researchers state, Aβ43 showed a higher propensity to aggregate and was more neurotoxic than Aβ42, which has to date been thought of as the main amyloidogenic and pathogenic agent in AD.
Takaomi C. Saido, Ph.D., and colleagues at Japan’s Riken Brain Science Institute, describes this research in Nature Neuroscience in a paper titled “Potent amyloidogenicity and pathogenicity of Aβ43.”
Building on independent research suggesting that Aβ43 appears to be as prone to aggregate in vitro as Aβ42, the team set out to investigate the possibility that Aβ43 may also contribute to AD pathology.
The researchers exploited a presenilin-1 (PS1) mutation known as R2781, which results in selective overproduction of Aβ43 in vitro and has also been found in patients with atypical forms of A