The idea of intraneuronal Aβ contributing to AD pathology certainly appears to be generating momentum, and this was evident at last month’s conference. Compelling evidence from new and established Aβ-related transgenic mouse models demonstrated that intraneuronal Aβ42 is an early event which precedes, and appears to correlate with, subsequent neuronal death. However, conflicting findings on postmortem AD brains on whether intraneuronal Aβ is an early event in AD, and is correlative with neuronal toxicity, needs to be resolved.

The evidence presented from the aforementioned transgenic mouse studies gives rise to a number of important questions that may have significant implications in understanding AD pathology. The first question that comes to mind is, what is the site and mechanism of toxicity induced by intraneuronal Aβ? And how does this differ from toxicity induced by the extracellular version? In addition, with increasing evidence for Aβ acting upstream of neurofibrillary tangle formation, it will be interesting to examine whether the neurons containing...  Read more

The idea of intraneuronal Aβ contributing to AD pathology certainly appears to be generating momentum, and this was evident at last month’s conference. Compelling evidence from new and established Aβ-related transgenic mouse models demonstrated that intraneuronal Aβ42 is an early event which precedes, and appears to correlate with, subsequent neuronal death. However, conflicting findings on postmortem AD brains on whether intraneuronal Aβ is an early event in AD, and is correlative with neuronal toxicity, needs to be resolved.

The evidence presented from the aforementioned transgenic mouse studies gives rise to a number of important questions that may have significant implications in understanding AD pathology. The first question that comes to mind is, what is the site and mechanism of toxicity induced by intraneuronal Aβ? And how does this differ from toxicity induced by the extracellular version? In addition, with increasing evidence for Aβ acting upstream of neurofibrillary tangle formation, it will be interesting to examine whether the neurons containing intracellular Aβ aggregates are prone to neurofibrillary tangle formation, as well. Despite the known spatial disparity between amyloid plaques and neurofibrillary tangles, the paradigm for intracellular Aβ pathology does not preclude the notion that amyloid and neurofibrillary pathology may exist in one and the same neuron.

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