Alzheimer's disease (AD) is characterized in part by the deposition of amyloid β protein (Aβ) in compact fibrillar plaques. These structures can induce an innate immune response in the brain, which triggers progressive inflammation, neuronal loss, and further acceleration of Aβ plaque formation. Compared with the case in normal individuals, the T and B lymphocytes in AD patients and murine models are hyporesponsive to Aβ. However, depending on the route of delivery, tolerance can be overcome by vaccination, with the induction of an anti-Aβ-mediated immune response. Through mechanisms that are incompletely understood, immunized APP transgenic animals show markedly reduced Aβ deposition, preservation of normal neuronal architecture, and improved performance in memory and spatial learning tasks. In human trials, Aβ vaccination stabilized cognition and slowed the progression of dementia. Neuropathologic examination of a vaccinated subject showed reduced cortical Aβ without changes in other AD-associated pathology. However, in some patients, vaccination induced severe meningoencephalitis, causing the trial to be terminated. Thus, vaccination appears to activate both beneficial and deleterious anti-Aβ immunity, suggesting that the vaccine can have potent clinical utility if an appropriate immunologic response can be generated.
- APP transgenic mice
- Alzheimer's disease
- Amyloid β protein
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience