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Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2

By Ruiben Feng, Huimin Wang, Jianlin Wang, David Shrom, Xuemei Zeng and Joe Z. Tsien

Abstract

Early-onset familial Alzheimer's disease is the most aggressive form of Alzheimer's, striking patients as early as their 30s; those patients typically carry mutations in presenilin-1 and presenilin-2. To investigate the coordinated functions of presenilin in the adult brain, we generated double knockout mice, in which both presenilins were deleted in the forebrain. We found that concurrent loss of presenilins in adulthood resulted in massive cortical shrinkage, atrophy of hippocampal molecular layers and corpus callosum, and enlargement of the lateral and third ventricles. We further revealed that deficiency of presenilins caused a series of biochemical alterations, including neuronal atrophy, astrogliosis, caspase-3-mediated apoptosis, and tau hyperphosphorylation. Thus, our study demonstrates that presenilins are essential for the ongoing maintenance of cortical structures and function

Topics: Biological Sciences
Publisher: National Academy of Sciences
Year: 2004
DOI identifier: 10.1073/pnas.0402733101
OAI identifier: oai:pubmedcentral.nih.gov:419574
Provided by: PubMed Central
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