TY - JOUR
T1 - Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2
AU - Feng, Ruiben
AU - Wang, Huimin
AU - Wang, Jianlin
AU - Shrom, David
AU - Zeng, Xuemei
AU - Tsien, Joe Z.
PY - 2004/5/21
Y1 - 2004/5/21
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0402733101
DO - 10.1073/pnas.0402733101
M3 - Article
C2 - 15148382
AN - SCOPUS:2542626705
SN - 0027-8424
VL - 101
SP - 8162
EP - 8167
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -