{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/891"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/891","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Genetic Reduction of Cholesterol Synthesis in the Mouse Brain Does Not Affect Amyloid Formation in an Alzheimer’s Disease Model, but Does Extend Lifespan","abstract":"In vitro alterations in cellular cholesterol content or synthesis affect the cleavage of amyloid precursor protein (APP) to amyloidogenic peptides characteristic of Alzheimer’s disease (AD). To determine whether a decrease in cholesterol synthesis would affect APP processing in vivo, we crossed cholesterol 24-hydroxylase knockout (KO) mice, which exhibit a 50 percent reduction in sterol synthesis, with transgenic mice (B6.Cg-Tg(APPswe, PSEN1E9)85Dbo/J) that develop AD and followed progression of the disease and lipid metabolism in the offspring. APP expression and amyloid plaque deposition in the cortex and hippocampus of 3- to 15-month-old male and female AD mice were similar in the presence and absence of cholesterol 24-hydroxylase. At 15 months of age, a modest but statistically significant decline in insoluble A-beta 40 and A-beta 42 peptide levels was detected in the hippocampus but not cortex of KO/AD mice versus WT/AD mice. Amyloid plaque accumulation did not affect brain sterol or fatty acid synthesis rates in 24-hydroxylase WT or KO mice. Unexpectedly, loss of one or two 24-hydroxylase alleles increased longevity in AD mice. These studies suggest that reducing de novo cholesterol synthesis in the brain will not substantially alter the course of AD, but may confer a survival advantage.","abstract_html":"In vitro alterations in cellular cholesterol content or synthesis affect the cleavage of amyloid precursor protein (APP) to amyloidogenic peptides characteristic of Alzheimer’s disease (AD). To determine whether a decrease in cholesterol synthesis would affect APP processing in vivo, we crossed cholesterol 24-hydroxylase knockout (KO) mice, which exhibit a 50 percent reduction in sterol synthesis, with transgenic mice (B6.Cg-Tg(APPswe, PSEN1E9)85Dbo/J) that develop AD and followed progression of the disease and lipid metabolism in the offspring. APP expression and amyloid plaque deposition in the cortex and hippocampus of 3- to 15-month-old male and female AD mice were similar in the presence and absence of cholesterol 24-hydroxylase. At 15 months of age, a modest but statistically significant decline in insoluble A-beta 40 and A-beta 42 peptide levels was detected in the hippocampus but not cortex of KO/AD mice versus WT/AD mice. Amyloid plaque accumulation did not affect brain sterol or fatty acid synthesis rates in 24-hydroxylase WT or KO mice. Unexpectedly, loss of one or two 24-hydroxylase alleles increased longevity in AD mice. These studies suggest that reducing de novo cholesterol synthesis in the brain will not substantially alter the course of AD, but may confer a survival advantage.","abstract_has_math":false,"creators":["Warren, Rebekkah Lynn"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Russell, David W."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-08-26T17:35:30Z","date_published":"2011-08-26T17:35:30Z","updated_at":"2026-07-24T05:52:20Z","subjects":["Amyloid beta-Protein Precursor","Alzheimer Disease","Lipid Metabolism"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["759117278"],"render_values":[{"text":"759117278","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/891","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Russell, David W."]},{"key":"dc:creator","label":"Author","values":["Warren, Rebekkah Lynn"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-08-26T17:35:30Z","2011-08-10"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Amyloid beta-Protein Precursor","Alzheimer Disease","Lipid Metabolism"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/891","759117278"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["In vitro alterations in cellular cholesterol content or synthesis affect the cleavage of amyloid precursor protein (APP) to amyloidogenic peptides characteristic of Alzheimer’s disease (AD). To determine whether a decrease in cholesterol synthesis would affect APP processing in vivo, we crossed cholesterol 24-hydroxylase knockout (KO) mice, which exhibit a 50 percent reduction in sterol synthesis, with transgenic mice (B6.Cg-Tg(APPswe, PSEN1E9)85Dbo/J) that develop AD and followed progression of the disease and lipid metabolism in the offspring. APP expression and amyloid plaque deposition in the cortex and hippocampus of 3- to 15-month-old male and female AD mice were similar in the presence and absence of cholesterol 24-hydroxylase. At 15 months of age, a modest but statistically significant decline in insoluble A-beta 40 and A-beta 42 peptide levels was detected in the hippocampus but not cortex of KO/AD mice versus WT/AD mice. Amyloid plaque accumulation did not affect brain sterol or fatty acid synthesis rates in 24-hydroxylase WT or KO mice. Unexpectedly, loss of one or two 24-hydroxylase alleles increased longevity in AD mice. These studies suggest that reducing de novo cholesterol synthesis in the brain will not substantially alter the course of AD, but may confer a survival advantage."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Genetic Reduction of Cholesterol Synthesis in the Mouse Brain Does Not Affect Amyloid Formation in an Alzheimer’s Disease Model, but Does Extend Lifespan"]}]}],"canonical_facts":{"dc:contributor":["Russell, David W."],"dc:creator":["Warren, Rebekkah Lynn"],"dc:date":["2011-08-26T17:35:30Z","2011-08-10"],"dc:description":["In vitro alterations in cellular cholesterol content or synthesis affect the cleavage of amyloid precursor protein (APP) to amyloidogenic peptides characteristic of Alzheimer’s disease (AD). To determine whether a decrease in cholesterol synthesis would affect APP processing in vivo, we crossed cholesterol 24-hydroxylase knockout (KO) mice, which exhibit a 50 percent reduction in sterol synthesis, with transgenic mice (B6.Cg-Tg(APPswe, PSEN1E9)85Dbo/J) that develop AD and followed progression of the disease and lipid metabolism in the offspring. APP expression and amyloid plaque deposition in the cortex and hippocampus of 3- to 15-month-old male and female AD mice were similar in the presence and absence of cholesterol 24-hydroxylase. At 15 months of age, a modest but statistically significant decline in insoluble A-beta 40 and A-beta 42 peptide levels was detected in the hippocampus but not cortex of KO/AD mice versus WT/AD mice. Amyloid plaque accumulation did not affect brain sterol or fatty acid synthesis rates in 24-hydroxylase WT or KO mice. Unexpectedly, loss of one or two 24-hydroxylase alleles increased longevity in AD mice. These studies suggest that reducing de novo cholesterol synthesis in the brain will not substantially alter the course of AD, but may confer a survival advantage."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/891","759117278"],"dc:language":["en"],"dc:subject":["Amyloid beta-Protein Precursor","Alzheimer Disease","Lipid Metabolism"],"dc:title":["Genetic Reduction of Cholesterol Synthesis in the Mouse Brain Does Not Affect Amyloid Formation in an Alzheimer’s Disease Model, but Does Extend Lifespan"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-24T05:52:20Z"}