Potential immunotargets for Alzheimer's disease treatment strategies

Alzheimer's disease (AD) exerts a profound burden on public health worldwide. AD etiology is unknown, and research to understand its underlying pathology has produced agents for the management of symptoms, but not a cure for the disease. Most AD drugs were developed in response to research implicating fibrillar amyloid-β (Aβ) in AD neuropathology but result in only modest short-term improvements in cognitive function, so there is agreement that additional targets need to be investigated. Evidence has implicated the immune system in AD and immunotherapy as a potential approach to AD treatment. Accumulation of microglia and astrocytes has been observed around Aβ deposits and several reports implicate inflammatory mediators in AD pathology. Importantly, Aβ deposition has been found in the brains of AD patients and in aged people without dementia, but signs of neuroinflammation are found only in AD patients and not in normal aged individuals. Animal models suggest a complex role for immunomodulators in AD, namely, these mechanisms are likely to promote the same pathogenic processes that gave rise to them. To date, clinical trials with anti-inflammatories and other immunoregulators have not been successful, but available data strongly favor immunomodulation as a promising disease intervention strategy. This article reviews data that implicate various immunomodulators in AD and considers their potential application in the development of novel AD therapeutics. Currently, a deeper understanding of nervous-immune interactions during normal aging and at all stages of AD is needed. Continued research in AD inflammatory and immunoregulatory processes will increase both our understanding of disease mechanisms and the likelihood of discovering new therapeutic targets for AD.