Abstract
Alzheimer’s disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide. Currently, there is no cure or way to prevent this devastating disease. Extracellular plaques, containing various forms of amyloid-β protein (Aβ), and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated tau protein, are two major pathological hallmarks of the AD brain. Aggregation, deposition, and N-terminal modification of Aβ protein and tau phosphorylation and aggregation are thought to precede the onset of cognitive decline, which is better correlated with tangle formation and neuron loss. Active and passive vaccines against various forms of Aβ have shown promise in pre-clinical animal models. However, translating these results safely and effectively into humans has been challenging. Recent clinical trials showed little or no cognitive efficacy, possibly due to the fact that the aforementioned neurodegenerative processes most likely pre-existed in the patients well before the start of immunotherapy. Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease. In addition, efforts to immunize against tau and other AD-related targets are underway.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide
There is a rise in Neurofibrillary tangle (NFT) and neuron loss that correlates with mild changes in memory
An active vaccine induces a T cell response that can increase the risk of a deleterious immune response, especially, if the T cell recognizes the antigen as a self-protein
Summary
It is well accepted that Alzheimer’s disease pathogenesis begins years, if not decades, before the onset of clinical symptoms. Amyloid-lowering treatments (e.g., active and passive Aβ immunotherapy) have shown little or no cognitive benefit in moderate to severe AD patients, in whom the disease process had been underway for years. This suggests that removing amyloid cannot reverse cognitive deficits once significant neuronal damage has occurred. Author’s information CAL is an Associate Professor of Neurology at the Brigham and Women’s Hospital and Harvard Medical School in Boston, MA She has performed preclinical studies of Aβ immunotherapy in AD-like transgenic mouse models and aged non-human primates for more than 14 years
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