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Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis

Redwine, Jeffrey M. and Kosofsky, Barry and Jacobs, Russell E. and Games, Dora and Reilly, John F. and Morrison, John H. and Young, Warren G. and Bloom, Floyd E. (2003) Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis. Proceedings of the National Academy of Sciences of the United States of America, 100 (3). pp. 1381-1386. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:REDpnas03

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Abstract

High-resolution magnetic resonance microscopy (MRM) was used to determine regional brain volumetric changes in a mouse model of Alzheimer's disease. These transgenic (Tg) mice overexpress human mutant amyloid precursor protein (APP) V717F under control of platelet-derived growth factor promoter (PDAPP mice), and cortical and hippocampal beta-amyloid (Abeta) deposits accumulate in heterozygotes after 8-10 mos. We used MRM to obtain 3D volumetric data on mouse brains imaged in their skulls to define genotype- and age-related changes. Hippocampal, cerebellar, and brain volumes and corpus callosum length were quantified in 40-, 100-, 365-, and 630-day-old mice. Measurements taken at age 100 days, before A(beta) deposition, revealed a 12.3% reduction of hippocampus volume in Tg mice compared with WT controls. This reduction persisted without progression to age 21 mos. A significant 18% increase in hippocampal volume occurred between 40 and 630 days in WT mice, and no corresponding significant increase occurred in Tg mice. Cavalieri volume estimates of hippocampal subfields from 100-day-old Tg mice further localized a 28% volume deficit in the dentate gyrus. In addition, corpus callosum length was reduced by approximate to 25% in Tg mice at all ages analyzed. In summary, reduced hippocampal volume and corpus callosum length can be detected by MIRM before Abeta deposition. We conclude that overexpression of APP and amyloid may initiate pathologic changes before the appearance of plaques, suggesting novel targets for the treatment of Alzheimer's disease and further reinforcing the need for early diagnosis and treatment.


Item Type:Article
Additional Information:Copyright © 2003 by the National Academy of Sciences. Contributed by Floyd E. Bloom, December 6, 2002. Published online before print January 24, 2003, 10.1073/pnas.242746599 We thank Trevor McCardle for excellent technical assistance with tissue preparation and Patrick R. Hof for helpful suggestions on the manuscript.
Subject Keywords:AMYLOID-PRECURSOR PROTEIN, FAMILIAL ALZHEIMERS-DISEASE, CORPUS-CALLOSUM ATROPHY, LONG-TERM POTENTIATION, TRANSGENIC MICE, HIPPOCAMPAL-NEURONS, BETA-PROTEIN, SYNAPTIC TRANSMISSION, IN-VIVO, ENTORHINAL CORTEX
Record Number:CaltechAUTHORS:REDpnas03
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:REDpnas03
Alternative URL:http://dx.doi.org/10.1073/pnas.242746599
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1073
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:16 Dec 2005
Last Modified:26 Dec 2012 08:42

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