Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive cognitive and behavioral problems resulting from a build-up of amyloid-beta (Aβ) plaques in the brain. The degree of neuropathology is partially related to apolipoprotein E (apoE), a fat-binding protein involved in transporting cholesterol to neurons. The APOE gene, which codes for the production of apoE, has several alleles in humans, including APOE3 (E3; the most common) and APOE4 (E4; which is associated with a high risk for developing AD). Transgenic mouse models of AD are commonly used to study the neuropathological processes behind the development of Aβ plaques, neurodegeneration, and associated behavioral deficits. The current study was designed to determine whether expression of E4 in a transgenic mouse model of AD (the PDAPP mouse) alters these processes in a way that replicates the effects observed in humans with E4. The brains of male PDAPP x APOE3 mice (PDAPP:E3; n=5) were compared to those of PDAPP x APOE4 mice (PDAPP:E4; n=4) by staining tissue sections with HJ3.4, thioflavin-S, and 4’,6-diamidino-2-phenylindole (DAPI) to quantify diffuse Aβ, fibrillar Aβ, and cellular count, respectively. PDAPP:E4 mice had more total Aβ in the CA1 of the hippocampus and dorsal cortex. Also, a trend suggested PDAPP:E4 mice had a lower cellular density in the CA1 and dorsal cortex than PDAPP:E3 mice. Importantly, more Alzheimer’s-like neuropathology was generally associated with worse behavioral deficits. Since these results replicate aspects of human AD (plaque load, lower cellular density, and behavioral deficits), the expression of human APOE in transgenic mice may improve their use as a model system for understanding the processes involved in the development of AD and therapeutic strategies for dealing with the disease.
","abstract_html":"<p>Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive cognitive and behavioral problems resulting from a build-up of amyloid-beta (Aβ) plaques in the brain. The degree of neuropathology is partially related to apolipoprotein E (apoE), a fat-binding protein involved in transporting cholesterol to neurons. The APOE gene, which codes for the production of apoE, has several alleles in humans, including APOE3 (E3; the most common) and APOE4 (E4; which is associated with a high risk for developing AD). Transgenic mouse models of AD are commonly used to study the neuropathological processes behind the development of Aβ plaques, neurodegeneration, and associated behavioral deficits. The current study was designed to determine whether expression of E4 in a transgenic mouse model of AD (the PDAPP mouse) alters these processes in a way that replicates the effects observed in humans with E4. The brains of male PDAPP x APOE3 mice (PDAPP:E3; n=5) were compared to those of PDAPP x APOE4 mice (PDAPP:E4; n=4) by staining tissue sections with HJ3.4, thioflavin-S, and 4’,6-diamidino-2-phenylindole (DAPI) to quantify diffuse Aβ, fibrillar Aβ, and cellular count, respectively. PDAPP:E4 mice had more total Aβ in the CA1 of the hippocampus and dorsal cortex. Also, a trend suggested PDAPP:E4 mice had a lower cellular density in the CA1 and dorsal cortex than PDAPP:E3 mice. Importantly, more Alzheimer’s-like neuropathology was generally associated with worse behavioral deficits. Since these results replicate aspects of human AD (plaque load, lower cellular density, and behavioral deficits), the expression of human APOE in transgenic mice may improve their use as a model system for understanding the processes involved in the development of AD and therapeutic strategies for dealing with the disease.</p>","abstract_has_math":false,"creators":["Halavi, Shina"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":"Psychology","degree_department":null,"school":null,"contributors":["Hartman, Richard E.","Haerich, Paul E.","Vermeersch, David A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-06-01T07:00:00Z","date_published":"2016-06-01T07:00:00Z","updated_at":"2026-07-24T02:52:45Z","subjects":["Clinical Psychology","Psychology","Social and Behavioral Sciences","Alzheimer's Disease - Pathology; Nervous System -- Pathophysiology; Amyloid-beta Peptides","Neuropathology; Neurodegenration; Plaque load; Cellular density; Behavioral deficits;"],"languages":["English"],"rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/394","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hartman, Richard E.","Haerich, Paul E.","Vermeersch, David A."]},{"key":"dc:creator","label":"Author","values":["Halavi, Shina"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Psychology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Clinical Psychology","Psychology","Social and Behavioral Sciences","Alzheimer's Disease - Pathology; Nervous System -- Pathophysiology; Amyloid-beta Peptides","Neuropathology; Neurodegenration; Plaque load; Cellular density; Behavioral deficits;"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/394"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive cognitive and behavioral problems resulting from a build-up of amyloid-beta (Aβ) plaques in the brain. The degree of neuropathology is partially related to apolipoprotein E (apoE), a fat-binding protein involved in transporting cholesterol to neurons. The APOE gene, which codes for the production of apoE, has several alleles in humans, including APOE3 (E3; the most common) and APOE4 (E4; which is associated with a high risk for developing AD). Transgenic mouse models of AD are commonly used to study the neuropathological processes behind the development of Aβ plaques, neurodegeneration, and associated behavioral deficits. The current study was designed to determine whether expression of E4 in a transgenic mouse model of AD (the PDAPP mouse) alters these processes in a way that replicates the effects observed in humans with E4. The brains of male PDAPP x APOE3 mice (PDAPP:E3; n=5) were compared to those of PDAPP x APOE4 mice (PDAPP:E4; n=4) by staining tissue sections with HJ3.4, thioflavin-S, and 4’,6-diamidino-2-phenylindole (DAPI) to quantify diffuse Aβ, fibrillar Aβ, and cellular count, respectively. PDAPP:E4 mice had more total Aβ in the CA1 of the hippocampus and dorsal cortex. Also, a trend suggested PDAPP:E4 mice had a lower cellular density in the CA1 and dorsal cortex than PDAPP:E3 mice. Importantly, more Alzheimer’s-like neuropathology was generally associated with worse behavioral deficits. Since these results replicate aspects of human AD (plaque load, lower cellular density, and behavioral deficits), the expression of human APOE in transgenic mice may improve their use as a model system for understanding the processes involved in the development of AD and therapeutic strategies for dealing with the disease.
"]},{"key":"dc:title","label":"Title","values":["Phenotyping Double Transgenic Mouse Models of Alzheimer’s that Express Human APP and ApoE3 or ApoE4"]}]}],"canonical_facts":{"dc:contributor":["Hartman, Richard E.","Haerich, Paul E.","Vermeersch, David A."],"dc:creator":["Halavi, Shina"],"dc:description.abstract":["Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive cognitive and behavioral problems resulting from a build-up of amyloid-beta (Aβ) plaques in the brain. The degree of neuropathology is partially related to apolipoprotein E (apoE), a fat-binding protein involved in transporting cholesterol to neurons. The APOE gene, which codes for the production of apoE, has several alleles in humans, including APOE3 (E3; the most common) and APOE4 (E4; which is associated with a high risk for developing AD). Transgenic mouse models of AD are commonly used to study the neuropathological processes behind the development of Aβ plaques, neurodegeneration, and associated behavioral deficits. The current study was designed to determine whether expression of E4 in a transgenic mouse model of AD (the PDAPP mouse) alters these processes in a way that replicates the effects observed in humans with E4. The brains of male PDAPP x APOE3 mice (PDAPP:E3; n=5) were compared to those of PDAPP x APOE4 mice (PDAPP:E4; n=4) by staining tissue sections with HJ3.4, thioflavin-S, and 4’,6-diamidino-2-phenylindole (DAPI) to quantify diffuse Aβ, fibrillar Aβ, and cellular count, respectively. PDAPP:E4 mice had more total Aβ in the CA1 of the hippocampus and dorsal cortex. Also, a trend suggested PDAPP:E4 mice had a lower cellular density in the CA1 and dorsal cortex than PDAPP:E3 mice. Importantly, more Alzheimer’s-like neuropathology was generally associated with worse behavioral deficits. Since these results replicate aspects of human AD (plaque load, lower cellular density, and behavioral deficits), the expression of human APOE in transgenic mice may improve their use as a model system for understanding the processes involved in the development of AD and therapeutic strategies for dealing with the disease.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/394"],"dc:language":["English"],"dc:rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."],"dc:subject":["Clinical Psychology","Psychology","Social and Behavioral Sciences","Alzheimer's Disease - Pathology; Nervous System -- Pathophysiology; Amyloid-beta Peptides","Neuropathology; Neurodegenration; Plaque load; Cellular density; Behavioral deficits;"],"dc:title":["Phenotyping Double Transgenic Mouse Models of Alzheimer’s that Express Human APP and ApoE3 or ApoE4"],"thesis:degree_discipline":["Psychology"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:52:45Z"}