Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease
A Monsonego, V Zota, A Karni, JI Krieger… - The Journal of clinical …, 2003 - jci.org
The Journal of clinical investigation, 2003•jci.org
Alzheimer disease (AD) is characterized by the progressive deposition of the 42-residue
amyloid β protein (Aβ) in brain regions serving memory and cognition. In animal models of
AD, immunization with Aβ results in the clearance of Aβ deposits from the brain. However, a
trial of vaccination with synthetic human Aβ1–42 in AD resulted in the development of
meningoencephalitis in some patients. We measured cellular immune responses to Aβ in
middle-aged and elderly healthy subjects and in patients with AD. A significantly higher …
amyloid β protein (Aβ) in brain regions serving memory and cognition. In animal models of
AD, immunization with Aβ results in the clearance of Aβ deposits from the brain. However, a
trial of vaccination with synthetic human Aβ1–42 in AD resulted in the development of
meningoencephalitis in some patients. We measured cellular immune responses to Aβ in
middle-aged and elderly healthy subjects and in patients with AD. A significantly higher …
Alzheimer disease (AD) is characterized by the progressive deposition of the 42-residue amyloid β protein (Aβ) in brain regions serving memory and cognition. In animal models of AD, immunization with Aβ results in the clearance of Aβ deposits from the brain. However, a trial of vaccination with synthetic human Aβ1–42 in AD resulted in the development of meningoencephalitis in some patients. We measured cellular immune responses to Aβ in middle-aged and elderly healthy subjects and in patients with AD. A significantly higher proportion of healthy elderly subjects and patients with AD had strong Aβ-reactive T cell responses than occurred in middle-aged adults. The immunodominant Aβ epitopes in humans resided in amino acids 16–33. Epitope mapping enabled the identification of MHC/T cell receptor (TCR) contact residues. The occurrence of intrinsic T cell reactivity to the self-antigen Aβ in humans has implications for the design of Aβ vaccines, may itself be linked to AD susceptibility and course, and appears to be associated with the aging process.
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