期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2006
卷号：103
期号：35
页码：13203-13207
DOI：10.1073/pnas.0605411103
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cognitive impairment has recently been found to correlate with changes in peripheral inflammatory signals such as TNF-{alpha} and IL-1[beta]. PKC isozymes regulate levels of TNF-{alpha} and IL-6 and the release of other cytokines and also show deficits in Alzheimer's disease (AD) brains and skin fibroblasts. Here, we investigate MAPK Erk1 and Erk2 phosphorylation in response to the inflammatory agonist bradykinin, which activates PKC pathways. An internally controlled comparison of Erk1 and Erk2 produced an AD index that accurately distinguished fibroblasts of AD from those of normal controls and of non-AD dementias. This accuracy was demonstrated for Coriell Cell Repository (Coriell Institute of Medical Research, Camden, NJ) samples, as well as for samples analyzed on gels with autopsy diagnostic confirmation. AD Erk1 and Erk2 index values were inversely correlated with disease duration, suggesting maximal efficacy for early diagnosis. Finally, the results also demonstrate that, when the AD index agreed with the clinical diagnosis on the presence of AD, there was a high probability of accuracy based on autopsy validation. Thus, this peripheral molecular biomarker, based on differential Erk1 and Erk2 phosphorylation, could have important clinical utility for providing increased certainty in the positive diagnosis of AD, particularly in the early phase of disease progression.
关键词：diagnostic ; MAPK ; Alzheimer’s index ; PKC ; human fibroblasts
