Gene expression profile of the PDAPP mouse model for Alzheimer's disease with and without Apolipoprotein E
Neurobiol Aging. ePub 2007 Sep 27
Selwood SP, Parvathy S, Cordell B, Ryan HS, Oshidari F, Vincent V, Yesavage J, Lazzeroni LC, Murphy GM Jr.
Neuroscience Research Laboratories, Stanford University School of Medicine, Stanford, CA, United States; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
The APOE varepsilon4 allele is a strong risk factor for Alzheimer's disease (AD). However, the molecular basis for this effect remains unclear. We examined expression of approximately 12,000 genes and expressed sequence tags in the hippocampus and cortex of PDAPP (APP(V717)) mice modeling AD that show extensive amyloid beta (Abeta) deposition, and in PDAPP mice lacking murine APOE expression, which show marked attenuation of Abeta deposition in the brain. Wild type and APOE knockout animals were also examined. Expression levels were determined at the initial stage of Abeta deposition, as well as in older animals showing extensive neuropathological changes. Fifty-four transcripts were identified using our statistical analysis as differentially regulated between the PDAPP and PDAPP/APOE ko mice, whereas 31 transcripts were classified as differentially regulated among PDAPP mice and WT animals, and seven transcripts were identified as regulated between the PDAPP/APOE ko animals and the APOE ko animals. Interestingly, many of the differentially regulated genes we detected can be related to biological processes previously shown to be important in AD pathophysiology, including inflammation, calcium homeostasis, cholesterol transport and uptake, kinases and phosphatases involved in tau phosphorylation and dephosphorylation, mitochondrial energy metabolism, protein degradation, neuronal growth, endoplasmic reticulum (ER) stress related proteins, antioxidant activity, cytoskeletal organization, and presenilin binding proteins. Regulated genes also included some not directly associated with AD in the past but likely to be involved in known AD pathophysiologic mechanisms, and others that may represent completely novel factors in the pathogenesis of AD. These results provide a global molecular profile of hippocampal and cortical gene expression during the initial and intermediate stages Abeta deposition, and the effects of APOE deletion on this process.
PubMed ID and Record
Selwood SP, Parvathy S, Cordell B, Ryan HS, Oshidari F, Vincent V, Yesavage J, Lazzeroni LC, Murphy GM Jr.
Neuroscience Research Laboratories, Stanford University School of Medicine, Stanford, CA, United States; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
The APOE varepsilon4 allele is a strong risk factor for Alzheimer's disease (AD). However, the molecular basis for this effect remains unclear. We examined expression of approximately 12,000 genes and expressed sequence tags in the hippocampus and cortex of PDAPP (APP(V717)) mice modeling AD that show extensive amyloid beta (Abeta) deposition, and in PDAPP mice lacking murine APOE expression, which show marked attenuation of Abeta deposition in the brain. Wild type and APOE knockout animals were also examined. Expression levels were determined at the initial stage of Abeta deposition, as well as in older animals showing extensive neuropathological changes. Fifty-four transcripts were identified using our statistical analysis as differentially regulated between the PDAPP and PDAPP/APOE ko mice, whereas 31 transcripts were classified as differentially regulated among PDAPP mice and WT animals, and seven transcripts were identified as regulated between the PDAPP/APOE ko animals and the APOE ko animals. Interestingly, many of the differentially regulated genes we detected can be related to biological processes previously shown to be important in AD pathophysiology, including inflammation, calcium homeostasis, cholesterol transport and uptake, kinases and phosphatases involved in tau phosphorylation and dephosphorylation, mitochondrial energy metabolism, protein degradation, neuronal growth, endoplasmic reticulum (ER) stress related proteins, antioxidant activity, cytoskeletal organization, and presenilin binding proteins. Regulated genes also included some not directly associated with AD in the past but likely to be involved in known AD pathophysiologic mechanisms, and others that may represent completely novel factors in the pathogenesis of AD. These results provide a global molecular profile of hippocampal and cortical gene expression during the initial and intermediate stages Abeta deposition, and the effects of APOE deletion on this process.
PubMed ID and Record
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