The aim of this article is to review the role of immunotherapy in the removal of proteins which accumulate abnormally in neurodegenerative disorders associated with dementia, in particular amyloid-β accumulation in Alzheimer's disease.
In both transgenic mouse models and in two trials of amyloid-β immunotherapy for human Alzheimer's disease, active immunization with amyloid-β 1-42 results in the removal of amyloid-β plaques from the cerebral cortex associated with, in the mouse models, improvement in cognitive function. Cerebral amyloid angiopathy and neurofibrillary tangles persist, however, and there is also concern about T lymphocyte immune reactions in the meninges in the human cases. Active immunization schedules are being developed to minimize T lymphocyte reactions and to maximize antibody production and passive immunization protocols are being devised. Immunotherapy for removal of the proteins which accumulate in other neurodegenerative disorders associated with dementia such as prion proteins and α-synuclein are in the early stages of development.
Dementias in the elderly are an increasing medical, social and economic problem and current treatments are only effective. In the majority of dementias, proteins accumulate within cells and in the extracellular compartments of the brain. In the most common dementia, Alzheimer's disease, amyloid-β accumulates as plaques in the extracellular space of the grey matter and in artery walls as cerebral amyloid angiopathy and tau protein accumulates as neurofibrillary tangles within neurons.
Abbreviations APP:amyloid precursor protein, CAA:cerebral amyloid angiopathy, ISF:interstitial fluid, NFT:neurofibrillary tangle, PrP:protease resistant protein
From the Division of Clinical Neurosciences, University of Southampton, School of Medicine, Southampton General Hospital, Southampton, SO166YD, UK.
Reprints:Delphine Boche, Division of Clinical Neurosciences, University of Southampton, Mailpoint 813, South Pathology Block, Southampton General Hospital, Southampton SO16 6YD, UK (e-mail: D.Boche@soton.ac.uk).
This article was originally published in Current Opinion in Neurology. It is reprinted here as a service to our readers. Delphine Bolche, James A.R. Nicoll and Roy O. Weller. Immunotheraphy for Alzheimer's disease and other dementias. Curr Opin Neurol 2005;118:720-725.