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Role of the Immune System in the Pathogenesis, Prevention and Treatment of Alzheimer’s Disease

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Abstract

The dysregulation in the metabolism of β-amyloid precursor protein and consequent deposition of amyloid-β (Aβ) has been envisaged as crucial for the development of neurodegeneration in Alzheimer’s disease (AD). Amyloid deposition begins 10–20 years before the appearance of clinical dementia. During this time, the brain is confronted with increasing amounts of toxic Aβ peptides and data from the last decade intriguingly suggest that both the innate and the adaptive immune systems may play an important role in the disorder.

Innate immunity in the brain is mainly represented by microglial cells, which phagocytose and degrade Aβ. As the catabolism of Aβ decreases, glial cells become overstimulated and start to produce substances that are toxic to neurons, such as nitric oxide and inflammatory proteins. Pro-inflammatory cytokines can be directly toxic or stimulate Aβ production and increase its cytotoxicity. A therapeutic possibility arises from clinical studies, which demonstrate that non-steroidal anti-inflammatory drugs (NSAIDs) may delay the onset and slow the progression of AD. Recent data show that in addition to the suppression of inflammatory processes in the brain NSAIDs may decrease the production of Aβ peptides.

The role of adaptive immunity lies mainly in the fact that Aβ can be recognised as an antigen. Immunisation with Aβ peptides and peripheral administration of Aβ-specific antibodies both decrease senile plaques and cognitive dysfunction in murine models of AD. A recent trial in humans seems still to be hampered by adverse effects. As adaptive immunity decreases with aging while innate immunity remains intact, immunotherapy for AD will have to be adapted to this situation. Strategies that combine vaccination and inflammatory drug treatment could be considered.

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Acknowledgements

The work was funded by the Austrian Federal Ministry of Education, Science and Culture (GZ 70.060/2-Pr/4/99), by the European Community (Project No QLRT-1999-02004 “MANAD”) and by Austrian Science Foundation (Project No P15347). The authors have provided no information on conflicts of interest directly relevant to the content of this review.

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  1. Department of Psychiatry, University Hospital of Innsbruck, Innsbruck, Austria

    Imrich Blasko

  2. Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, Innsbruck, A-6020, Austria

    Beatrix Grubeck-Loebenstein

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Blasko, I., Grubeck-Loebenstein, B. Role of the Immune System in the Pathogenesis, Prevention and Treatment of Alzheimer’s Disease. Drugs & Aging 20, 101–113 (2003). https://doi.org/10.2165/00002512-200320020-00002

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