Vaccination against Alzheimer disease An update on future strategies

摘要

Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer. Alzheimer vaccines Alzheimer Disease (AD) is an important progressive neurodegenerative illness, and is a major form of dementia. With increasing age, the probability to develop AD steeply increases and currently affects 26 million people worldwide. As the age of the human population is globally growing, the increased life expectancy and the consequent increased frequency and number of patients afflicted with this disease is becoming a large social and economic burden. Only symptomatic and not very effective treatments are currently available and in view of the alarming epidemiological data, novel therapeutic strategies to prevent, mitigate or delay the onset of AD are pursued extensively. The hallmark of the pathology observed in AD is plaques in the brain of the afflicted patients. Active or passive vaccination against components of these plaques is currently one of the most promising therapies with disease-modifying potential. The 2 major components of the plaques are extracellular aggregates of amyloid-beta (Abeta) peptides, which are cleaved out of the amyloid precursor protein (APP) by the beta- and gamma-secretase, and intracellular neurofibrillary tangles (NFT) consisting of hyperphosphorylated tau proteins. Under healthy conditions Abeta peptides as well as tau proteins are constantly expressed but do not show aggregate formation. The normal function of Abeta remains controversial but seems to have e.g., an anti-microbial activity. In contrast, tau proteins stabilize microtubules and ensure neuronal integrity and stimulus transfer.