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

Ruiben Feng, Huimin Wang, Jianlin Wang, David Shrom, Xuemei Zeng, Joseph Zhuo Tsien

Research output: Contribution to journalArticle

90 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8162-8167
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number21
DOIs
StatePublished - May 21 2004
Externally publishedYes

ASJC Scopus subject areas

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