[Significance of intracellular A beta in Alzheimer's disease].

It is now widely accepted that beta-amyloid has a central role in the pathogenesis of Alzheimer's disease (AD). It is mainly composed of aggregated A beta protein and is deposited in senile plaques and cerebral blood vessels. However, it is not uncommon to see autopsies that reveal significant deposits of beta-amyloid in the brain without manifesting dementia. In fact, several neuropathological studies showed no correlation between beta-amyloid burden and the severity of dementia or loss of synapses. Thus it is questioned whether extracellularly deposited beta-amyloid is directly linked to the Alzheimer pathomechanism. Here I show evidence to support the significance of intraneuronally deposited A beta x-42 by analyzing presenilin 1 transgenic mice and AD patients.