Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease
<p>Abstract</p> <p>Background</p> <p>Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny in clinical s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-09-01
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| Series: | Journal of Neuroinflammation |
| Online Access: | http://www.jneuroinflammation.com/content/7/1/57 |
| _version_ | 1811275604868202496 |
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| author | Bosetti Francesca Wetzel Ronald Dealwis Chris Prendergast Jay S Rebeck G William Mocchetti Italo Niikura Takako Aid Saba Shimoji Mika Sidahmed Elkhansa Minami S Sakura Matsuoka Yasuji Hoe Hyang-Sook Turner R Scott |
| author_facet | Bosetti Francesca Wetzel Ronald Dealwis Chris Prendergast Jay S Rebeck G William Mocchetti Italo Niikura Takako Aid Saba Shimoji Mika Sidahmed Elkhansa Minami S Sakura Matsuoka Yasuji Hoe Hyang-Sook Turner R Scott |
| author_sort | Bosetti Francesca |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny in clinical studies, but its application is limited by neuroinflammatory side effects (autoimmune encephalitis and vasogenic edema).</p> <p>Methods</p> <p>We intravenously administered the monoclonal Aβ protofibril antibody PFA1 to aged (22 month) male and female 3 × tg AD mice with intermediate or advanced AD-like neuropathologies, respectively, and measured brain and serum Aβ and CNS cytokine levels. We also examined 17 month old 3 × tg AD female mice with intermediate pathology to determine the effect of amyloid burden on responses to passive immunization.</p> <p>Results</p> <p>The 22 month old male mice immunized with PFA1 had decreased brain Aβ, increased serum Aβ, and no change in CNS cytokine levels. In contrast, 22 month old immunized female mice revealed no change in brain Aβ, decreased serum Aβ, and increased CNS cytokine levels. Identical experiments in younger (17 month old) female 3 × tg AD mice with intermediate AD-like neuropathologies revealed a trend towards decreased brain Aβ and increased serum Aβ accompanied by a decrease in CNS MCP-1.</p> <p>Conclusions</p> <p>These data suggest that passive immunization with PFA1 in 3 × tg AD mice with intermediate disease burden, regardless of sex, is effective in mediating potentially therapeutic effects such as lowering brain Aβ. In contrast, passive immunization of mice with a more advanced amyloid burden may result in potentially adverse effects (encephalitis and vasogenic edema) mediated by certain proinflammatory cytokines.</p> |
| first_indexed | 2024-04-12T23:41:57Z |
| format | Article |
| id | doaj.art-acb5dad78df74d0e9a48d02634907856 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-12T23:41:57Z |
| publishDate | 2010-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-acb5dad78df74d0e9a48d026349078562022-12-22T03:11:59ZengBMCJournal of Neuroinflammation1742-20942010-09-01715710.1186/1742-2094-7-57Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's diseaseBosetti FrancescaWetzel RonaldDealwis ChrisPrendergast Jay SRebeck G WilliamMocchetti ItaloNiikura TakakoAid SabaShimoji MikaSidahmed ElkhansaMinami S SakuraMatsuoka YasujiHoe Hyang-SookTurner R Scott<p>Abstract</p> <p>Background</p> <p>Passive immunization with antibodies directed to Aβ decreases brain Aβ/amyloid burden and preserves memory in transgenic mouse models of Alzheimer's disease (AD). This therapeutic strategy is under intense scrutiny in clinical studies, but its application is limited by neuroinflammatory side effects (autoimmune encephalitis and vasogenic edema).</p> <p>Methods</p> <p>We intravenously administered the monoclonal Aβ protofibril antibody PFA1 to aged (22 month) male and female 3 × tg AD mice with intermediate or advanced AD-like neuropathologies, respectively, and measured brain and serum Aβ and CNS cytokine levels. We also examined 17 month old 3 × tg AD female mice with intermediate pathology to determine the effect of amyloid burden on responses to passive immunization.</p> <p>Results</p> <p>The 22 month old male mice immunized with PFA1 had decreased brain Aβ, increased serum Aβ, and no change in CNS cytokine levels. In contrast, 22 month old immunized female mice revealed no change in brain Aβ, decreased serum Aβ, and increased CNS cytokine levels. Identical experiments in younger (17 month old) female 3 × tg AD mice with intermediate AD-like neuropathologies revealed a trend towards decreased brain Aβ and increased serum Aβ accompanied by a decrease in CNS MCP-1.</p> <p>Conclusions</p> <p>These data suggest that passive immunization with PFA1 in 3 × tg AD mice with intermediate disease burden, regardless of sex, is effective in mediating potentially therapeutic effects such as lowering brain Aβ. In contrast, passive immunization of mice with a more advanced amyloid burden may result in potentially adverse effects (encephalitis and vasogenic edema) mediated by certain proinflammatory cytokines.</p>http://www.jneuroinflammation.com/content/7/1/57 |
| spellingShingle | Bosetti Francesca Wetzel Ronald Dealwis Chris Prendergast Jay S Rebeck G William Mocchetti Italo Niikura Takako Aid Saba Shimoji Mika Sidahmed Elkhansa Minami S Sakura Matsuoka Yasuji Hoe Hyang-Sook Turner R Scott Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease Journal of Neuroinflammation |
| title | Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease |
| title_full | Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease |
| title_fullStr | Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease |
| title_full_unstemmed | Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease |
| title_short | Therapeutic versus neuroinflammatory effects of passive immunization is dependent on Aβ/amyloid burden in a transgenic mouse model of Alzheimer's disease |
| title_sort | therapeutic versus neuroinflammatory effects of passive immunization is dependent on aβ amyloid burden in a transgenic mouse model of alzheimer s disease |
| url | http://www.jneuroinflammation.com/content/7/1/57 |
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