M. Ward - Academia.edu (original) (raw)
Papers by M. Ward
Alzheimer's & Dementia, 2011
Background: Mitochondrial fission proteins dynamin-related protein (Drp1), S-nitrosylated Drp1 (S... more Background: Mitochondrial fission proteins dynamin-related protein (Drp1), S-nitrosylated Drp1 (SNO-Drp1) and Fis1 have been found altered in brain tissues and skin fibroblasts from patients with Alzheimer disease (AD), and some alterations are specific for AD. Peripheral blood lymphocytes (PBL) are attractive for biomarker discovery since some changes in PBL such as cell cycle reentry have been shown to reflect AD-specific changes in neurons. Therefore similar changes in mitochondrial fission proteins might also occur in PBL and these changes might be useful to discriminate AD patients. Methods: Western blot analysis and ELISA were employed to quantify relative levels of Drp1, SNO-Drp1 and Fis1 in PBL. Logistic regression was used to determine the predictive accuracy of measured proteins for the differentiation between AD and control subjects. Sensitivity and specificity of measured proteins were determined by the receiver operating characteristic (ROC) curve analysis. Results: Western blot analysis of 15 controls, 15 AD, 12 PD (Parkinson disease) and 12 VaD (vascular dementia) showed remarkable increases in the levels of SNO-Drp1 and Fis1 and decreased Drp1 in PBL from AD patients compared to controls, PD or VaD. ELISAs were used to measure these proteins from larger-size subjects including 91 controls (mean age 76.6 years) and 82 AD patients (mean age 77.6 years). Remarkable increases in the levels of Fis1 and SNO-Drp1 and a significant decrease in Drp1 were also detected in PBL of AD patients. Disease severity or duration had no effect on levels of these proteins in AD PBL. Results of the logistic regression analysis of ELISA data showed that these proteins discriminated AD patients significantly from control subjects. ROC curve analysis revealed that specificity and sensitivity were 85% and 82% for SNO-Drp1, 89% and 80% for Fis1 and 81% and 73% for Drp1 in identifying AD patients. The diagnostic accuracy of Drp1, SNO-Drp1 and Fis1 was 77%, 84% and 84%, respectively. Conclusions: Mitochondrial fission proteins Drp1, SNO-Drp1 and Fis1 were significantly altered in AD PBL compared to age-matched controls and allowed to identify AD patients from normal controls with high diagnostic accuracy. Thus these proteins may serve as biomarkers for AD diagnosis.
Alzheimer&amp... more Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant discussion, including potential next steps to move this area of research forward.
Alzheimer's & Dementia, 2011
Background: Mitochondrial fission proteins dynamin-related protein (Drp1), S-nitrosylated Drp1 (S... more Background: Mitochondrial fission proteins dynamin-related protein (Drp1), S-nitrosylated Drp1 (SNO-Drp1) and Fis1 have been found altered in brain tissues and skin fibroblasts from patients with Alzheimer disease (AD), and some alterations are specific for AD. Peripheral blood lymphocytes (PBL) are attractive for biomarker discovery since some changes in PBL such as cell cycle reentry have been shown to reflect AD-specific changes in neurons. Therefore similar changes in mitochondrial fission proteins might also occur in PBL and these changes might be useful to discriminate AD patients. Methods: Western blot analysis and ELISA were employed to quantify relative levels of Drp1, SNO-Drp1 and Fis1 in PBL. Logistic regression was used to determine the predictive accuracy of measured proteins for the differentiation between AD and control subjects. Sensitivity and specificity of measured proteins were determined by the receiver operating characteristic (ROC) curve analysis. Results: Western blot analysis of 15 controls, 15 AD, 12 PD (Parkinson disease) and 12 VaD (vascular dementia) showed remarkable increases in the levels of SNO-Drp1 and Fis1 and decreased Drp1 in PBL from AD patients compared to controls, PD or VaD. ELISAs were used to measure these proteins from larger-size subjects including 91 controls (mean age 76.6 years) and 82 AD patients (mean age 77.6 years). Remarkable increases in the levels of Fis1 and SNO-Drp1 and a significant decrease in Drp1 were also detected in PBL of AD patients. Disease severity or duration had no effect on levels of these proteins in AD PBL. Results of the logistic regression analysis of ELISA data showed that these proteins discriminated AD patients significantly from control subjects. ROC curve analysis revealed that specificity and sensitivity were 85% and 82% for SNO-Drp1, 89% and 80% for Fis1 and 81% and 73% for Drp1 in identifying AD patients. The diagnostic accuracy of Drp1, SNO-Drp1 and Fis1 was 77%, 84% and 84%, respectively. Conclusions: Mitochondrial fission proteins Drp1, SNO-Drp1 and Fis1 were significantly altered in AD PBL compared to age-matched controls and allowed to identify AD patients from normal controls with high diagnostic accuracy. Thus these proteins may serve as biomarkers for AD diagnosis.
Alzheimer&amp... more Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers. In April 2012, the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation convened top scientists from around the world to discuss the state of blood based biomarker development. This manuscript summarizes the meeting and the resultant discussion, including potential next steps to move this area of research forward.