Comparison of Aβ levels in the brain of familial and sporadic Alzheimer's disease

Mutations in presenilin (PS) and amyloid precursor protein (APP) genes are a predominant cause for early-onset familial Alzheimer disease (AD). Although these mutations are rare, they have in the past decades advanced our understanding of the underlying molecular mechanisms of AD. In the present study, A beta levels were measured in cortical regions of APPsw and PSI (M146V) mutation carriers, sporadic AD (SAD) and age-matched non-demented individuals. We found similar levels of soluble A beta 42, insoluble and soluble A beta 40 in both APPsw mutation carriers and SAD. However, lower levels of insoluble A beta 42 were detected in the frontal and temporal cortex of APPsw brain. In PSI brain, insoluble A beta 40 and A beta 42 levels were significantly lower in all four cortical regions compared with SAD, whilst levels of A beta 42 were lower in frontal and occipital cortex compared with APPsw brain. The insoluble A beta 42/40 ratio was similar in SAD and APPsw but significantly higher in PSI mutation carriers. Our results indicate that the pattern of A beta deposition in PSI mutation carriers differs from that in both APPsw and SAD, whereas the pattern in APPsw mutation carriers is more similar to that in SAD. (C) 2009 Elsevier Ltd. All rights reserved.