Alzheimer disease (AD) is a neurodegenerative disease characterized by a decline in cognitive function. The two major pathological features of this disease include extracellular β-amyloid (Aβ) plaques and intraneural neurofibrillary tangles. These pathological features seem to appear years before cognitive symptoms.1 Several hypotheses relate the pathological deteriorations in the brain of patients with AD to the mechanisms of neural degeneration. Among them, the amyloid hypothesis has emerged as a critical determinant of this pathology.2 According to this hypothesis, the neural degeneration that occurs in AD-affected brains is the consequence of Aβ hyperproduction and accumulation, resulting in Aβ deposits and leading to neuronal death. Since its proposal more than 15 years ago, numerous reports have strengthened the hypothesis that Aβ is the primary initiator of AD, but there are also many reports demonstrating that AD does not conform exactly to the amyloid hypothesis. For example, even though the total level of Aβ is elevated in AD, it does not correlate well with disease severity. In this issue of the Archives, Steinerman et al3 demonstrate that the solubility and compartmentalization of Aβ in the brain, rather than the total amount of Aβ, may serve as a better predictor of AD symptoms.
Sephton CF, Yu G. Abeta Predictor of Alzheimer Disease Symptoms. Arch Neurol. 2008;65(7):875–876. doi:10.1001/archneur.65.7.875
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