Immunological approaches for amyloid-beta clearance toward treatment for Alzheimer's disease

Research output: Contribution to journalReview articlepeer-review

Abstract

The pathology of Alzheimer's disease is characterized primarily by extracellular plaques and intracellular neurofibrillary tangles. Plaques are composed mainly of the amyloid-beta peptide, whereas tangles are derived from the cytoskeletal protein tau. The most studied hypothesis of development of the disease is that of the amyloid cascade, which states that overproduction of amyloid-beta peptide, or failure to clear this peptide, leads to Alzheimer's disease primarily through amyloid deposition, which is presumed to be involved in neurofibrillary tangle formation; these lesions are then associated with cell death, which is reflected in memory impairment, the hallmarks of this dementia. We developed a new concept showing that site-directed antibodies against amyloid-beta peptide may modulate formation of amyloid filaments, which has become the theoretical basis of the immunological approach for treatment of Alzheimer's disease. The performance of anti-beta-amyloid antibodies in transgenic mouse models of Alzheimer's disease showed they are delivered to the central nervous system, clearing amyloid plaques and protecting the mice from learning and age-related memory deficits. Amyloid plaque clearance via specific anti-amyloid-beta peptide antibodies follows multiple mechanisms. As immunotherapy is at the crossroads of immunology and the nervous system, a deeper understanding of the amyloid-beta peptide clearance mechanism may lead to an optimized therapeutic approach to the treatment of Alzheimer's disease. Antibodies generated with the first-generation vaccine might not have the desired therapeutic properties to target the "correct" mechanism, however, new immunological approaches are now under consideration.

Original languageEnglish
Pages (from-to)349-357
Number of pages9
JournalRejuvenation Research
Volume11
Issue number2
DOIs
StatePublished - 1 Apr 2008

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