ArticleProceedings of the National Academy of Sciences of the United States of America2003
Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: a magnetic resonance microscopy and stereologic analysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 203 citations in OpenAlex.
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- Magnetic Resonance Imaging in Animal Models of Alzheimer's Disease Amyloidosis.International journal of molecular sciences · 2021Review
- Hippocampal neurobiology and function in an aged mouse model of TDP-43 proteinopathy in an APP/PSEN1 background.Neuroscience letters · 2021Article
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- Anatomical variations of the dentate gyrus in normal adult brain.Surgical and radiologic anatomy : SRA · 2020Article
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- Quantitative study of the capillaries within the white matter of the Tg2576 mouse model of Alzheimer's disease.Brain and behavior · 2019Article
- Anti-aggregant tau mutant promotes neurogenesis.Molecular neurodegeneration · 2017Article
- Post-natal Deletion of Neuronal cAMP Responsive-Element Binding (CREB)-1 Promotes Pro-inflammatory Changes in the Mouse Hippocampus.Neurochemical research · 2017Article
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7 more citing papers are in PubMed but not listed here.
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8 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
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 Abeta 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 approximately 25% in Tg mice at all ages analyzed. In summary, reduced hippocampal volume and corpus callosum length can be detected by MRM 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.
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