Premium
O3‐04‐03: Association of plasma Aβ with risk of dementia: The prospective 3C‐study
Author(s) -
Lambert JeanCharles,
ShcraenMaschke Susanna,
Richard Florence,
Fievet Nathalie,
Rouaud Olivier,
Berr Claudine,
Dartigues JeanFrançois,
Tzourio Christophe,
Alpérovitch Annick,
Amouyel Philippe
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.05.450
Subject(s) - dementia , prospective cohort study , hazard ratio , medicine , cohort , biomarker , vascular dementia , cohort study , proportional hazards model , alzheimer's disease , disease , confidence interval , chemistry , biochemistry
fitted to the PIB data wherein a panel of 18 plasma protein spots could successfully discriminate individuals in the ‘high’ and ‘low’ DVR groups. Furthermore, these 18 protein spots accounted for approximately 60% of variance in mean cortical PIB deposition in the combined cohort. Further cross validation was performed by permutation response testing and confirmed robust predictive ability of the original PLS-DA model. Liquid chromatography tandem mass spectrometry (LC/MS/MS) was used to confirm the identities of these protein spots. Conclusions: Using this novel approach combining proteomic analysis of plasma with [C]-PIB PET of the brain, we have identified a panel of plasma proteins predictive of amyloid burden in the aging brain. These proteins hold considerable promise as antecedent markers of AD neuropathology and merit validation in larger datasets. tions between inflammatory and trophic factors at the peripheral level, as well as their potential influence on clinical manifestations of AD were investigated. Methods: Serum levels of TNF-alpha, soluble TNF receptors (sTNF-RI and II), IL-6, total and free IGF-I were determined by ELISA methods; and the correlations of these factors with cognitive performance and disability scores were evaluated in AD, mild cognitive impairment (MCI) and elderly control subjects (EC). Results: Serum levels of TNFalpha, sTNF-RI and IL-6 were increased (p < 0.01) and total IGF-I values reduced (p < 0.01) in AD patients as compared with controls. Circulating TNF-alpha and IL-6 correlated negatively with total and free IGF-I, and positively with disability scores in AD patients. Cognitive performance (MMSE) scores showed week but significant negative correlations with TNF-alpha, sTNF-RI and IL-6, and a positive correlation with IGF-I only in the whole sample. Conclusions: According to our results, peripheral inflammatory biomarkers (TNF-alpha, sTNF-RI and IL-6) are overexpressed in AD, seem to have a negative influence on the production of the neurotrophic factor IGF-I, and are associated with a worsen performance of AD patients in activities of daily living. These results support the involvement of proinflammatory factors in AD pathophysiology and suggest the potential utility of the determination of peripheral inflammation biomarkers in AD clinical trials.