Humoral immunity in brain aging and Alzheimer's disease

Constantin Bouras, Beat M. Riederer, Enikö Kövari, Patrick R. Hof, Panteleimon Giannakopoulos

Research output: Contribution to journalReview articlepeer-review

59 Scopus citations

Abstract

Although the contribution of inflammatory processes in the etiology of late-onset Alzheimer's disease (AD) has been suspected for years, most studies were confined to the analysis of cell-mediated immunological reactions thought to represent an epiphenomenon of AD lesion development. Based on the traditional view of the "immunological privilege" of the brain, which excludes a direct access of human immunoglobulins (Ig) to the central nervous system under normal conditions, little attention has been paid to a possible role of humoral immunity in AD pathogenesis. In the first part of this review, we summarize evidences for a blood-brain barrier (BBB) dysfunction in this disorder and critically comment on earlier observations supporting the presence of anti-brain autoantibodies and immunoglobulins (Ig) in AD brains. Current concepts regarding the Ig turnover in the central nervous system and the mechanisms of glial and neuronal Fc receptors activation are also discussed. In the second part, we present new ex vivo and in vitro data suggesting that human immunoglobulins can interact with tau protein and alter both the dynamics and structural organization of microtubules. Subsequent experiments needed to test this new working hypothesis are addressed at the end of the review.

Original languageEnglish
Pages (from-to)477-487
Number of pages11
JournalBrain Research Reviews
Volume48
Issue number3
DOIs
StatePublished - Jun 2005

Keywords

  • Brain aging
  • Cytoskeleton
  • Immunoglobulins
  • Microtubules
  • Neurodegeneration
  • Tau

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