Tau-targeted treatment strategies in Alzheimer's disease

Jürgen Götz*, Arne Ittner, Lars M. Ittner

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

98 Citations (Scopus)

Abstract

With populations ageing worldwide, the need for treating and preventing diseases associated with high age is pertinent. Alzheimer's disease (AD) is reaching epidemic proportions, yet the currently available therapies are limited to a symptomatic relief, without halting the degenerative process that characterizes the AD brain. As in AD cholinergic neurons are lost at high numbers, the initial strategies were limited to the development of acetylcholinesterase inhibitors, and more recently the NMDA receptor antagonist memantine, in counteracting excitotoxicity. With the identification of the protein tau in intracellular neurofibrillary tangles and of the peptide amyloid-β (Aβ) in extracellular amyloid plaques in the AD brain, and a better understanding of their role in disease, newer strategies are emerging, which aim at either preventing their formation and deposition or at accelerating their clearance. Interestingly, what is well established to combat viral diseases in peripheral organs - vaccination - seems to work for the brain as well. Accordingly, immunization strategies targeting Aβ show efficacy in mice and to some degree also in humans. Even more surprising is the finding in mice that immunization strategies targeting tau, a protein that forms aggregates in nerve cells, ameliorates the tau-associated pathology. We are reviewing the literature and discuss what can be expected regarding the translation into clinical practice and how the findings can be extended to other neurodegenerative diseases with protein aggregation in brain.

Original languageEnglish
Pages (from-to)1246-1259
Number of pages14
JournalBritish Journal of Pharmacology
Volume165
Issue number5
DOIs
Publication statusPublished - 1 Mar 2012
Externally publishedYes

Keywords

  • learning and memory
  • neuropharmacology
  • neuroprotective drugs
  • synaptic plasicity
  • therapeutic antibodies

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