EXOGENOUS INDUCTION OF ALZHEIMER A?-PATHOLOGY IN TRANSGENIC MICE

转基因小鼠中阿尔茨海默病 A 型病理的外源诱导

• 批准号: 7715846
• 负责人: LARY C WALKER
• 金额: $ 2.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715846
• 关键词: APP-PS1; Alzheimer' s Disease; Animals; Antibodies; Brain; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Confocal Microscopy; Contralateral; Deposition; Enzyme-Linked Immunosorbent Assay; Funding; Grant; Hippocampus (Brain); Human; Immunofluorescence Immunologic; Immunoprecipitation; Injection of therapeutic agent; Institution; MALDI-TOF Mass Spectrometry; Mus; Pathology; Patients; Pattern; Peptides; Population; Primates; Research; Research Personnel; Resistance; Resources; Saimiri; Seeds; Source; Testing; Transgenic Mice; United States National Institutes of Health; aged; internal control

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have examined the quantitative and qualitative characteristics of A¿ in humans with AD and in squirrel monkeys (Saimiri sciureus), a closely related, but AD-resistant, primate species. By ELISA, we found that cortical A¿ levels in aged squirrel monkeys can equal or exceed the levels in AD brain. Using immunoprecipitation and MALDI-TOF mass spectrometry, we have also shown that soluble and insoluble A¿ peptide populations are highly similar in squirrel monkeys and humans with AD. To test the hypothesis that A¿-multimers in the two species may assume pathogenically dissimilar forms, we then examined the ability of A¿-rich cortical extracts from squirrel monkeys and AD patients to induce, or seed, A¿ deposition in APP/PS1 transgenic mice. Dilute cortical extracts were injected unilaterally into the hippocampus of APP/PS1 mice, prior to the endogenous deposition of A¿ in that region. Sham PBS injections in the contralateral hemisphere served as internal controls. After a 4 month incubation period, the mouse brains were immunostained with antibodies to the A¿ peptide. A¿ deposition was enhanced in the extract-injected hemisphere of all experimental animals. With double immunofluorescence and confocal microscopy, we identified cellular and parenchymal patterns of seeded A¿ deposition unique to AD and squirrel monkey extracts.

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