Recently, researchers from Tsinghua University used a highly-purified recombinant γ-secretase and recombinant rat proteins to detect the effect of 128 AD-derived presenilin-1 (PS1) mutations on the production of β amyloid (Aβ42 and Aβ40). The results were published in the December 5 issue of the Proceedings of the National Academy of Sciences (PNAS). It is Professor Yigong Shi of Tsinghua University who led the study.

One of the signs of Alzheimer's disease (AD) is that amyloid protein (Aβ) in the brain of the patient is aggregated into amyloid plaques. Amyloid precursor protein (APP) is cleaved by intracellular membrane protease γ secretion, resulting in a length of Aβ, where longer peptides (e.g., β42) are considered to be harmful. Increasing the ratio of longer Aβs to make it more than short Aβs, for example, increasing the ratio of β42 to Aβ40 may lead to the formation of amyloid plaques and the consequent development of AD.

Another important indicator of AD development is the mean age of onset (AAO) for patients with PS1, PS2 or APP co-mutations. A more harmful mutation may be reflected in the lower AAO. The analysis of mutations in a small proportion of AD leads to a strong correlation: the higher the Aβ42 / Aβ40 ratio, the lower the AAO. In contrast, a different set of PS1 mutations showed only weak correlations. It is noteworthy that these conclusions are derived from a limited number of mutations, lacking statistical significance.

In this study, the authors reconstituting the mutated PS1 proteins into γ-secretases that contained APH-1aL and detected their ability to produce Aβ42 and Aβ40 in vitro, analyzing 138 reported human PS1 mutations. Approximately 90% of these mutations can result in a reduction in Aβ42 and Aβ40 production. It is noteworthy that 10% of these mutations can result in a decrease in the ratio of Aβ42 / Aβ40. There was no statistically significant association between the Aβ42/Aβ40 ratio produced by the γ-secretase variant containing a specific PS1 mutation and the mean morbidity age of the patients (the mutation was isolated from their body). By the way, Flarebio provides you with superior recombinant proteins such as recombinant ITGB5.