Reduced expression of amyloid precursor protein, presenilin-1 and rab3a incortical brain regions in Alzheimer's disease

To study the role of amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease (AD), the level of APP was analysed by quantitative im munoblotting in 6 AD patients and 6 age-matched controls in 9 brain regions . These were associative cortices (orbital frontal cortex, inferior tempora l cortex, inferior parietal cortex), primary cortex (occipital cortex), lim bic structures (anterior cingulate gyrus, hippocampus), subcortical structu res (putamen, thalamus) and cerebellum. To assess a potential relationship between APP and presenilin-1 (PS-1) and/or synaptic proteins, the levels of PS-1 and rab3a, a specific synaptic vesicle protein, were also determined in the same tissue samples. The level of APP was almost the same in the ass ociation cortical regions, primary cortex, and limbic structures and in the subcortical structures, while the lowest level was found in the cerebellum . There were more marked differences in the level of PS-1 and rab3a between different brain regions. The highest levels of PS-1 and rab3a were found i n the association cortical areas, while intermediate levels were found in p rimary cortex, limbic structures and subcortical structures. As for APP, th e lowest level was found in cerebellum. We found significantly reduced leve ls of all three proteins in the association cortices and in hippocampus in AD. Our data show that the protein levels are reduced in specific areas, re stricted to neuronal populations that are known to degenerate in AD. Due to the similarity of the expression of APP, PS-1 and rab3a, it is tempting to speculate whether there is a functional relationship between these protein s. Copyright (C) 2001 S. Karger AG, Basel.