The effect of presenilin-1 on cerebral amyloid protein

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The effect of presenilin-1 on cerebral amyloid b proteinAmyloid beta protein (Abeta) in senile plaque and amyloid angiopathy is important not only for neuropathological hallmarker but also for the causal gene (APP) product. The possible interaction of APP and presenilin-1, another causal gene localized on chromosome 14, becomes the crutial issue for the etiology of the disease. Here we analyzed the effect of presenilin-1 on cerebral Abeta deposition in patients with Alheimer's disease.Abeta is composed of Abeta1-4O and Abeta1-42/43. Accumulating evidence shows that the causal mutation of presenilin-1 induces the higher concentration of Abeta1-42/43 than Abeta1-40. However, the present analysis showed also that the mutation causes significantly higher Abeta1-40 in addition to Abeta1-42/43 in AD patients. This may be related with the recent findings on multiple function for presenilm-1 that (1) presenhlin-1 null mice show both defects on Abeta1 production and developmental segmentation, (2) presenilin-1 could bind APP, beta-catenin and GSK3beta molecules. Thus, it is highly likely that presenilin-l affect both Abeta species. This remains to be studied using transgenic mouse model in future.