CD4 T cells in immunity and immunotherapy of Alzheimer's disease

Alon Monsonego, Anna Nemirovsky, Idan Harpaz

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common form of dementia, with prevalence progressively increasing with aging. Pathological hallmarks of the disease include accumulation of amyloid β-protein (Aβ) peptides and neurofibrillary tangles in the brain associated with glial activation and synaptotoxicity. In addition, AD involves peripheral and brain endogenous inflammatory processes that appear to enhance disease progression. More than a decade ago a new therapeutic paradigm emerged for AD, namely the activation of the adaptive immune system directly against the self-peptide Aβ, aimed at lowering its accumulation in the brain. This was the first time that a brain peptide was used to vaccinate human subjects in a manner similar to classic viral or bacterial vaccines. The vaccination approach has taken several forms, from initially active to passive and then back to modified active vaccines. As the first two approaches to date failed to show sufficient efficacy, the last is presently being evaluated in ongoing clinical trials. The present review summarizes the immunogenic characteristics of Aβ in humans and mice and discusses past, present and future Aβ-based immunotherapeutic approaches for AD. We emphasize potential pathogenic and beneficial roles of CD4 T cells in light of the pathogenesis and the general decline in T-cell responsiveness evident in the disease.

Original languageEnglish
Pages (from-to)438-446
Number of pages9
JournalImmunology
Volume139
Issue number4
DOIs
StatePublished - 1 Aug 2013

Keywords

  • Alzheimer's disease
  • Amyloid β-protein (Aβ)
  • Aβ antibodies
  • CD4 T cells
  • Immunotherapy

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