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An amyloid-beta protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer's disease.
Lord, Anna; Gumucio, Astrid; Englund, Hillevi; Sehlin, Dag; Sundquist, Valentina Screpanti; Söderberg, Linda; Möller, Christer; Gellerfors, Pär; Lannfelt, Lars; Pettersson, Frida Ekholm; Nilsson, Lars N G.
Afiliação
  • Lord A; Department of Public Health and Caring Sciences/Molecular Geriatrics, Uppsala University, Rudbeck Laboratory, Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
Neurobiol Dis ; 36(3): 425-34, 2009 Dec.
Article em En | MEDLINE | ID: mdl-19703562
Human genetics link Alzheimer's disease pathogenesis to excessive accumulation of amyloid-beta (Abeta) in brain, but the symptoms do not correlate with senile plaque burden. Since soluble Abeta aggregates can cause synaptic dysfunctions and memory deficits, these species could contribute to neuronal dysfunction and dementia. Here we explored selective targeting of large soluble aggregates, Abeta protofibrils, as a new immunotherapeutic strategy. The highly protofibril-selective monoclonal antibody mAb158 inhibited in vitro fibril formation and protected cells from Abeta protofibril-induced toxicity. When the mAb158 antibody was administered for 4 months to plaque-bearing transgenic mice with both the Arctic and Swedish mutations (tg-ArcSwe), Abeta protofibril levels were lowered while measures of insoluble Abeta were unaffected. In contrast, when treatment began before the appearance of senile plaques, amyloid deposition was prevented and Abeta protofibril levels diminished. Therapeutic intervention with mAb158 was however not proven functionally beneficial, since place learning depended neither on treatment nor transgenicity. Our findings suggest that Abeta protofibrils can be selectively cleared with immunotherapy in an animal model that display highly insoluble Abeta deposits, similar to those of Alzheimer's disease brain.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Doença de Alzheimer / Amiloide / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Neurobiol Dis Assunto da revista: NEUROLOGIA Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Suécia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos beta-Amiloides / Doença de Alzheimer / Amiloide / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Neurobiol Dis Assunto da revista: NEUROLOGIA Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Suécia