Deficits in Reelin expression and signaling play a pathogenic role in Alzheimer’s disease (AD). Thus, strategies aimed at correcting Reelin deficits may provide a novel therapeutic approach to treating AD. The cysteine-rich, whey protein supplement, Immunocal®, has recently been shown to rescue Reelin expression in a mouse model of Schizophrenia. Given that Reelin-expressing neurons of the entorhinal cortex region are a highly vulnerable population of cells that are lost early in AD, we examined the effects of Immunocal® in the hippocampal-entorhinal cortex formation in a mouse model of AD. Glutathione levels and Reelin expression in the hippocampal-entorhinal cortex formation (entorhinal cortex, EC; dentate gyrus, DG; and Cornu Ammonis, CA1/ Cornu Ammonis, CA3 regions of hippocampus) of 12-month old hAPPSweInd mice were significantly reduced when compared to non-carrier controls as measured by HPLC, western blot and immunohistochemistry respectively. These reductions were prevented in hAPPSweInd mice when treated with Immunocal® from 3 month to 12-month-old. We assessed the transcript levels of Reelin using in situ hybridization and show a reduction in Reelin transcript levels in untreated hAPPSweInd mice compared to non-carrier mice; However, Immunocal® treatment preserved Reelin transcript levels. Elevating Reelin expression through treatment with Immunocal® significantly reduced the number, size and density of Amyloglo stained amyloid plaques throughout the hippocampal-entorhinal cortex formation. Our findings demonstrate that Immunocal® rescues Reelin expression in vivo within the hippocampal-entorhinal cortex formation of 12-month-old transgenic hAPPSweInd mice. This rescue of Reelin expression was associated with an amelioration of the pathological amyloid plaque load. To our knowledge, these data provide the first evidence of a therapeutic agent that is capable of correcting Reelin deficits in the hAPPSweInd mouse model of AD. Our findings support the testing of Immunocal® as a novel therapeutic agent for patients suffering from Alzheimer’s disease.
","abstract_html":"<p>Deficits in Reelin expression and signaling play a pathogenic role in Alzheimer’s disease (AD). Thus, strategies aimed at correcting Reelin deficits may provide a novel therapeutic approach to treating AD. The cysteine-rich, whey protein supplement, Immunocal®, has recently been shown to rescue Reelin expression in a mouse model of Schizophrenia. Given that Reelin-expressing neurons of the entorhinal cortex region are a highly vulnerable population of cells that are lost early in AD, we examined the effects of Immunocal® in the hippocampal-entorhinal cortex formation in a mouse model of AD. Glutathione levels and Reelin expression in the hippocampal-entorhinal cortex formation (entorhinal cortex, EC; dentate gyrus, DG; and Cornu Ammonis, CA1/ Cornu Ammonis, CA3 regions of hippocampus) of 12-month old hAPPSweInd mice were significantly reduced when compared to non-carrier controls as measured by HPLC, western blot and immunohistochemistry respectively. These reductions were prevented in hAPPSweInd mice when treated with Immunocal® from 3 month to 12-month-old. We assessed the transcript levels of Reelin using in situ hybridization and show a reduction in Reelin transcript levels in untreated hAPPSweInd mice compared to non-carrier mice; However, Immunocal® treatment preserved Reelin transcript levels. Elevating Reelin expression through treatment with Immunocal® significantly reduced the number, size and density of Amyloglo stained amyloid plaques throughout the hippocampal-entorhinal cortex formation. Our findings demonstrate that Immunocal® rescues Reelin expression in vivo within the hippocampal-entorhinal cortex formation of 12-month-old transgenic hAPPSweInd mice. This rescue of Reelin expression was associated with an amelioration of the pathological amyloid plaque load. To our knowledge, these data provide the first evidence of a therapeutic agent that is capable of correcting Reelin deficits in the hAPPSweInd mouse model of AD. Our findings support the testing of Immunocal® as a novel therapeutic agent for patients suffering from Alzheimer’s disease.</p>","abstract_has_math":false,"creators":["Puttagunta, Srivalli"],"institution":null,"degree_name":"M.S.","degree_level":"Masters Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Martin Margittai, Ph.D.","Robert Dores, Ph.D.","Yan Qin, Ph.D.","Daniel Linseman, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-01-01T08:00:00Z","date_published":"2019-01-01T08:00:00Z","updated_at":"2026-07-24T02:02:11Z","subjects":["Aging","Alzheimer's disease","Immunocal","Neurodegeneration","Oxidative stress","Reelin","Biochemistry","Biotechnology","Life Sciences"],"languages":["en"],"rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.du.edu/etd/1683","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Martin Margittai, Ph.D.","Robert Dores, Ph.D.","Yan Qin, Ph.D.","Daniel Linseman, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Puttagunta, Srivalli"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2020-01-21T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Aging","Alzheimer's disease","Immunocal","Neurodegeneration","Oxidative stress","Reelin","Biochemistry","Biotechnology","Life Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright is held by the author. User is responsible for all copyright compliance.
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"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Amelioration of Alzheimer's Disease Pathology in 12-Month-Old hAPP(SweInd) Transgenic Mice After Treatment with a Cysteine Rich Whey Supplement, Immunocal®"]}]}],"canonical_facts":{"dc:contributor":["Martin Margittai, Ph.D.","Robert Dores, Ph.D.","Yan Qin, Ph.D.","Daniel Linseman, Ph.D."],"dc:creator":["Puttagunta, Srivalli"],"dc:date.available":["2020-01-21T08:00:00Z"],"dc:description.abstract":["Deficits in Reelin expression and signaling play a pathogenic role in Alzheimer’s disease (AD). Thus, strategies aimed at correcting Reelin deficits may provide a novel therapeutic approach to treating AD. The cysteine-rich, whey protein supplement, Immunocal®, has recently been shown to rescue Reelin expression in a mouse model of Schizophrenia. Given that Reelin-expressing neurons of the entorhinal cortex region are a highly vulnerable population of cells that are lost early in AD, we examined the effects of Immunocal® in the hippocampal-entorhinal cortex formation in a mouse model of AD. Glutathione levels and Reelin expression in the hippocampal-entorhinal cortex formation (entorhinal cortex, EC; dentate gyrus, DG; and Cornu Ammonis, CA1/ Cornu Ammonis, CA3 regions of hippocampus) of 12-month old hAPPSweInd mice were significantly reduced when compared to non-carrier controls as measured by HPLC, western blot and immunohistochemistry respectively. These reductions were prevented in hAPPSweInd mice when treated with Immunocal® from 3 month to 12-month-old. We assessed the transcript levels of Reelin using in situ hybridization and show a reduction in Reelin transcript levels in untreated hAPPSweInd mice compared to non-carrier mice; However, Immunocal® treatment preserved Reelin transcript levels. Elevating Reelin expression through treatment with Immunocal® significantly reduced the number, size and density of Amyloglo stained amyloid plaques throughout the hippocampal-entorhinal cortex formation. Our findings demonstrate that Immunocal® rescues Reelin expression in vivo within the hippocampal-entorhinal cortex formation of 12-month-old transgenic hAPPSweInd mice. This rescue of Reelin expression was associated with an amelioration of the pathological amyloid plaque load. To our knowledge, these data provide the first evidence of a therapeutic agent that is capable of correcting Reelin deficits in the hAPPSweInd mouse model of AD. Our findings support the testing of Immunocal® as a novel therapeutic agent for patients suffering from Alzheimer’s disease.
"],"dc:format":["application/pdf"],"dc:identifier":["https://digitalcommons.du.edu/etd/1683"],"dc:language":["en"],"dc:rights":["Copyright is held by the author. User is responsible for all copyright compliance.
"],"dc:subject":["Aging","Alzheimer's disease","Immunocal","Neurodegeneration","Oxidative stress","Reelin","Biochemistry","Biotechnology","Life Sciences"],"dc:title":["Amelioration of Alzheimer's Disease Pathology in 12-Month-Old hAPP(SweInd) Transgenic Mice After Treatment with a Cysteine Rich Whey Supplement, Immunocal®"],"thesis:degree_level":["Masters Thesis"],"thesis:degree_name":["M.S."]},"updated_at":"2026-07-24T02:02:11Z"}