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The path to next-generation disease-modifying immunomodulatory combination therapies in Alzheimer's disease.
Sarazin, Marie; Lagarde, Julien; El Haddad, Inès; de Souza, Leonardo Cruz; Bellier, Bertrand; Potier, Marie-Claude; Bottlaender, Michel; Dorothée, Guillaume.
Afiliação
  • Sarazin M; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte-Anne, Paris, France. m.sarazin@ghu-paris.fr.
  • Lagarde J; Université Paris-Cité, Paris, France. m.sarazin@ghu-paris.fr.
  • El Haddad I; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot, CEA, CNRS, Inserm, Orsay, France. m.sarazin@ghu-paris.fr.
  • de Souza LC; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte-Anne, Paris, France.
  • Bellier B; Université Paris-Cité, Paris, France.
  • Potier MC; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot, CEA, CNRS, Inserm, Orsay, France.
  • Bottlaender M; Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, Immune System and Neuroinflammation Laboratory, Hôpital Saint-Antoine, Paris, France.
  • Dorothée G; Grupo de Pesquisa em Neurologia Cognitiva e do Comportamento, Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Nat Aging ; 4(6): 761-770, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38839924
ABSTRACT
The cautious optimism following recent anti-amyloid therapeutic trials for Alzheimer's disease (AD) provides a glimmer of hope after years of disappointment. Although these encouraging results represent discernible progress, they also highlight the need to enhance further the still modest clinical efficacy of current disease-modifying immunotherapies. Here, we highlight crucial milestones essential for advancing precision medicine in AD. These include reevaluating the choice of therapeutic targets by considering the key role of both central neuroinflammation and peripheral immunity in disease pathogenesis, refining patient stratification by further defining the inflammatory component within the forthcoming ATN(I) (amyloid, tau and neurodegeneration (and inflammation)) classification of AD biomarkers and defining more accurate clinical outcomes and prognostic biomarkers that better reflect disease heterogeneity. Next-generation immunotherapies will need to go beyond the current antibody-only approach by simultaneously targeting pathological proteins together with innate neuroinflammation and/or peripheral-central immune crosstalk. Such innovative immunomodulatory combination therapy approaches should be evaluated in appropriately redesigned clinical therapeutic trials, which must carefully integrate the neuroimmune component.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Imunoterapia Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Imunoterapia Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article