Abstract
Amyloid plaques consist primarily of a 40–42 amino acid peptide called amyloid-β (Aβ) that is aggregated in fibrils that contain a high β-sheet structure. Plaques become insoluble and deposit within the brain extracellular space. Amyloid plaques are typically associated with swollen, dystrophic neurites, astrogliosis, and activated microglia, which together comprise a neuritic plaque. In contrast to amyloid plaques, neurofibrillary tangles accumulate intracellularly within neurons. Amyloid plaques and neurofibrillary tangles are hallmark pathologies that characterize Alzheimer's disease (AD). Accumulation of the amyloid-β (Aβ) peptide in different aggregated conformations within the brain is central to the pathogenesis of Alzheimer's disease (AD). In brains of AD patients, amyloid plaques are surrounded by swollen, dystrophic neurites. Particular aggregated species of Aβ are also toxic to neurons and are proposed to inhibit synaptic transmission. In order to prevent or reverse Aβ-related pathology, several therapeutic strategies are aimed at reducing brain Aβ levels. Both active and passive immunization strategies have been demonstrated to significantly reduce the amount of Aβ plaques and the associated neuritic dystrophy within the brain as well as reverse behavioral deficits in animal models of disease. In 2002, a clinical trial in humans using active immunization against the Aβ peptide was halted early due to adverse side effects, including death, in a subset of individuals. Importantly however, there was a hint that there may be cognitive benefits as well as reduced amyloid pathology in response to immunization. Immunization strategies are currently being designed to target specific aspects of the immune response in order to minimize or prevent adverse side effects while still reducing Aβ levels and ameliorating disease symptoms.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call