Abstract：
:Mutations of the presenilin-1 gene are a major cause of familial early-onset Alzheimer's disease. Presenilin-1 can associate with members of the catenin family of signalling proteins, but the significance of this association is unknown. Here we show that presenilin-1 forms a complex with beta-catenin in vivo that increases beta-catenin stability. Pathogenic mutations in the presenilin-1 gene reduce the ability of presenilin-1 to stabilize beta-catenin, and lead to increased degradation of beta-catenin in the brains of transgenic mice. Moreover, beta-catenin levels are markedly reduced in the brains of Alzheimer's disease patients with presenilin-1 mutations. Loss of beta-catenin signalling increases neuronal vulnerability to apoptosis induced by amyloid-beta protein. Thus, mutations in presenilin-1 may increase neuronal apoptosis by altering the stability of beta-catenin, predisposing individuals to early-onset Alzheimer's disease.
journal_name
Naturejournal_title
Natureauthors
Zhang Z,Hartmann H,Do VM,Abramowski D,Sturchler-Pierrat C,Staufenbiel M,Sommer B,van de Wetering M,Clevers H,Saftig P,De Strooper B,He X,Yankner BAdoi
10.1038/27208subject
Has Abstractpub_date
1998-10-15 00:00:00pages
698-702issue
6703eissn
0028-0836issn
1476-4687journal_volume
395pub_type
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