tailieunhanh - Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer’s disease

Using the CalSIM model, we predict changes in coverage in California as a result of the ACA. Take up of available coverage options in the model is based on a wide range of factors, including the pre-policy starting point, health status, household income, change in cost to purchase coverage, and English proficiency. For Medi-Cal, we assume that 61 percent of uninsured newly eligible individuals, and 10 percent of those who were previously eligible but not enrolled, enroll under our base scenario. is assumption is based on current Medi-Cal take up in the For the enhanced scenario we follow the Urban Institute/Kaiser Family Foundation9 enhanced participation estimate and assume that 75 percent of. | Stomrud et al. Alzheimer s Research Therapy 2010 2 20 http content 2 3 20 alzheimer s researchtherapy RESEARCH Open Access Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer s disease Erik Stomrud1 2 Maria Bjorkqvist3 Sabina Janciauskiene4 Lennart Minthon1 2 Oskar Hansson1 2 Abstract Introduction Matrix metalloproteinases MMP are believed to be involved in the pathologic processes behind Alzheimer s disease AD . In this study we aimed to examine the cerebrospinal fluid CSF levels of MMPs and tissue inhibitors of metalloproteinase-1 TIMP-1 in individuals with AD dementia and cognitively healthy elderly individuals and to investigate their relationship with established CSF biomarkers for Alzheimer s disease. Methods CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1 MMP-3 MMP-9 TIMP-1 p-amyloid1-42 Ap42 total tau protein T-tau and phosphorylated tau protein P-tau . MMP TIMP-1 ratios were calculated. APOE genotype was determined for the participants. Results AD patients had higher MMP-9 TIMP-1 ratios and lower TIMP-1 levels compared to cognitively healthy individuals. In AD patients the MMP-9 TIMP-1 ratio correlated with CSF T-tau a marker of neurodegeneration. Interestingly the cognitively healthy individuals with risk markers for future AD . AD-supportive CSF biomarker levels of T-tau P-tau and Ap42 or the presence of the APOE e4 allele had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3 TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels. Conclusions This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive .