- Email: [email protected]
FREQUENCY OF THE BUTYRYLCHOLINESTERASE WILD-TYPE GENOTYPE IN ALZHEIMER'S PATIENTS NOT TREATED WITH RIVASTIGMINE
Poster Presentations: P3
Figure 2. VEGF-A levels in the serum of patients of AD without depression, AD with depression, and control subjects There were no significant difference in VEGF-A levels in the serum among patients with AD without depression, AD with depression, and control subjects. (F (2,72) ¼ 2.385, p > .05) according to the presence of depression in Alzheimer’s disease. These results suggested the pathophysiology and progression of Alzheimer’s disease might be altered if depression may be occured or combined in AD. P3-116
FREQUENCY OF THE BUTYRYLCHOLINESTERASE WILD-TYPE GENOTYPE IN ALZHEIMER’S PATIENTS NOT TREATED WITH RIVASTIGMINE
Georg Adler, Nadja Baumgart, Angelika Mautes, ISPG, Mannheim, Germany. Contact e-mail: [email protected] Background: In advanced stages of Alzheimer’s disease (AD), butyrylcholinesterase (BuChE) progressively replaces acetylcholinesterase (AChE) in the hydrolysis of acetylcholine. This applies particularly in AD patients with the genetic variant of the BuChE wild-type, which has a higher hydrolysis rate than the frequent BuChE K-variant and is associated with a faster progression of dementia. Rivastigmine is the only commercially available AChE inhibitor, which also inhibits BuChE. Thus it may have advantages over the other AChE inhibitors, particularly in patients with BuChE wildtype. In the present study, we determined the proportion of patients with BuChE wild-type in a group of AD out-patients not treated with rivastigmine. Methods: In a multicentric study, the BuChE genotype was examined in AD patients with progressing dementia, who had no antidementive treatment or who were under treatment with either donepezil, galantamine or memantine. Results: The study was conducted in 126 AD patients (48 men, 78 women) at ages between 57 and 94 years (mean/SD: 79.2/7.3 years); MMSE score ranged between 4 and 27 (mean/SD: 17.8/5.7). The patients were treated with either donepezil (n¼58), memantine (n¼29) or galantamin (N¼22); 17 patients were not under antidementive medication. The BuChE wild-type was found in 95 (75.4 %) of the patients, in 89 (70.6 %) in the heterozygous and in 6 (4.8 %) in the homozygous genotype. Conclusions: We found the BuChE wild-type in 75 % of AD patients with progressing dementia, who were not under treatment with the BuChE inhibitor rivastigmine. In these patients, a switch of antidementive medication to rivastigmine or the initiation of rivastigmine treatment seem to be advisable. P3-117
EMPLOYING LYMPHOCYTE PROLIFERATION AS A MEANS TO ASSESS CELL CYCLE DYSREGULATION IN COGNITIVELY IMPAIRED SUBJECTS: ANALYTICAL PERFORMANCE OF THE LYMPRO ASSAY
Gerald Commissiong, Amarantus Bioscience Holdings, Inc., San Fransisco, California, United States. Contact e-mail: tiffini.clark@ amarantus.com Background: Initial studies by Thomas Arendt et.al, at the University of Leipzig identified the mitogenic response of peripheral blood lymphocytes
P671
(PLB) as a potential biomarker of Alzheimer’s disease (AD) [Stieler, JT, and Arendt, T.; et al. Neuroreport 2001; 12(18):3969-3972]. This finding was confirmed in a second study conducted by AAA, where the authors were able to retrospectively differentiate AD from Other Dementias [(OD), mostly Idiopathic Parkinson’s disease] with 95% sensitivity and 90% specificity [Steiler, J et al, 2012. Neurobio Aging 33:234-341]. Methods: Analytical performance of this flow cytometer assay was re-established at a contract GLP laboratory. In collaboration with clinicians, patient blood was sampled and purified for PBMCs. Following the published protocol, a stimulation index was established for CD69 positive expression following mitogenic stimulation. Experiments were conducted on health volunteer blood specimens to assess analytical performance characteristics of the assay. Both variance and effect size were assessed in health normal subjects. Results: Analytical performance data shows excellent reproducibility with coefficients of variation less than 20% for most mitogenic conditions. Additional performance metrics like effect of gating parameters and reagent stability were quantified. The effect of pre-analytical variables such as sample handing conditions will be presented as well. Conclusions: The LymPro test, which measures mitogenic response to peripheral blood lymphocytes, is demonstrating suitable analytical performance for use in a fit-for-purpose fashion in the Company’s hands. P3-118
RETROSPECTIVE ANALYSIS OF CLINICAL PROGNOSIS OF SUBJECTS FROM A 2005 STUDY USING THE LYMPRO ASSAY
Gerald Commissiong, Amarantus Bioscience Holdings, Inc., San Francisco, California, United States. Contact e-mail: tiffini.clark@ amarantus.com Background: Initial studies by Thomas Arendt et.al, at the University of Leipzig identified the mitogenic response of peripheral blood lymphocytes (PLB) as a potential biomarker of Alzheimer’s disease (AD)[Stieler, JT, and Arendt, T.; et al. Neuroreport 2001; 12(18):3969-3972]. This finding was confirmed in a second study conducted by AAA, where the authors were able to retrospectively differentiate AD from Other Dementias [(OD), mostly Idiopathic Parkinson’s disease] with 95% sensitivity and 90% specificity [Steiler, J et al, 2012. Neurobio Aging 33:234-341]. Clinical followup of the second cohort of patients was followed up over the past 8 years. Methods: Review of the existing clinical records of the subjects who participated in the Neurobio of Aging study provide an opportunistic cohort of subjects with which to begin to assess the LymPro assay for any potential prognostic utility. In particular, looking at the healthy normal controls and seeing which if any progressed would be of primary interest. Of secondary interest, review of the patients in the AD or PDD groups may provide insight into further development within a disease severity. In particular, biomarker ends points from the 2005 assay were assessed for their ability to correctly predict progression to cognitive impairment or other indications within each of the 3 sub-cohorts of subjects (N¼28 controls, N¼xx, Alzheimer’s disease patients, N¼yy Parkinson disease patients). Logistic regression was used for categorical endpoints whereas proportional-hazard models were used when time-to-event data were available. Results: Review of the 8 years of clinical records of the N¼ 28 control subjects from the original study reveals interesting prognostic information gleaned from the original wet biology biomarkers. In particular, two markers to be presented show hints of prognostic utility with weak statistical significance. Conclusions: Retrospective analysis of the prospective clinical records of participants in the 2005 LymPro study provide an opportunistic look at the prognostic value of the LymPro assay results. Although the sample size is small, individual markers within various lymphocyte subpopulations were assessed as candidate prognostic markers, some with weakly significant results. These results suggest that further evaluation in larger sample sizes is worthwhile. P3-119
STUDY OF DNA METHYLATION OF APP AND APOE GENES IN A SAMPLE OF COLOMBIAN ALZHEIMER’S DISEASE
Hernan G. Hernandez1, Adriana Marcela Mejia1, Maria Fernanda Mahecha1, Rodrigo Pardo1, Gonzalo Arboleda1, Juan Jose Yunis1, Diego Forero2, Humberto Arboleda1, 1UNAL, Bogota,
Figure 2. VEGF-A levels in the serum of patients of AD without depression, AD with depression, and control subjects There were no significant difference in VEGF-A levels in the serum among patients with AD without depression, AD with depression, and control subjects. (F (2,72) ¼ 2.385, p > .05) according to the presence of depression in Alzheimer’s disease. These results suggested the pathophysiology and progression of Alzheimer’s disease might be altered if depression may be occured or combined in AD. P3-116
FREQUENCY OF THE BUTYRYLCHOLINESTERASE WILD-TYPE GENOTYPE IN ALZHEIMER’S PATIENTS NOT TREATED WITH RIVASTIGMINE
Georg Adler, Nadja Baumgart, Angelika Mautes, ISPG, Mannheim, Germany. Contact e-mail: [email protected] Background: In advanced stages of Alzheimer’s disease (AD), butyrylcholinesterase (BuChE) progressively replaces acetylcholinesterase (AChE) in the hydrolysis of acetylcholine. This applies particularly in AD patients with the genetic variant of the BuChE wild-type, which has a higher hydrolysis rate than the frequent BuChE K-variant and is associated with a faster progression of dementia. Rivastigmine is the only commercially available AChE inhibitor, which also inhibits BuChE. Thus it may have advantages over the other AChE inhibitors, particularly in patients with BuChE wildtype. In the present study, we determined the proportion of patients with BuChE wild-type in a group of AD out-patients not treated with rivastigmine. Methods: In a multicentric study, the BuChE genotype was examined in AD patients with progressing dementia, who had no antidementive treatment or who were under treatment with either donepezil, galantamine or memantine. Results: The study was conducted in 126 AD patients (48 men, 78 women) at ages between 57 and 94 years (mean/SD: 79.2/7.3 years); MMSE score ranged between 4 and 27 (mean/SD: 17.8/5.7). The patients were treated with either donepezil (n¼58), memantine (n¼29) or galantamin (N¼22); 17 patients were not under antidementive medication. The BuChE wild-type was found in 95 (75.4 %) of the patients, in 89 (70.6 %) in the heterozygous and in 6 (4.8 %) in the homozygous genotype. Conclusions: We found the BuChE wild-type in 75 % of AD patients with progressing dementia, who were not under treatment with the BuChE inhibitor rivastigmine. In these patients, a switch of antidementive medication to rivastigmine or the initiation of rivastigmine treatment seem to be advisable. P3-117
EMPLOYING LYMPHOCYTE PROLIFERATION AS A MEANS TO ASSESS CELL CYCLE DYSREGULATION IN COGNITIVELY IMPAIRED SUBJECTS: ANALYTICAL PERFORMANCE OF THE LYMPRO ASSAY
Gerald Commissiong, Amarantus Bioscience Holdings, Inc., San Fransisco, California, United States. Contact e-mail: tiffini.clark@ amarantus.com Background: Initial studies by Thomas Arendt et.al, at the University of Leipzig identified the mitogenic response of peripheral blood lymphocytes
P671
(PLB) as a potential biomarker of Alzheimer’s disease (AD) [Stieler, JT, and Arendt, T.; et al. Neuroreport 2001; 12(18):3969-3972]. This finding was confirmed in a second study conducted by AAA, where the authors were able to retrospectively differentiate AD from Other Dementias [(OD), mostly Idiopathic Parkinson’s disease] with 95% sensitivity and 90% specificity [Steiler, J et al, 2012. Neurobio Aging 33:234-341]. Methods: Analytical performance of this flow cytometer assay was re-established at a contract GLP laboratory. In collaboration with clinicians, patient blood was sampled and purified for PBMCs. Following the published protocol, a stimulation index was established for CD69 positive expression following mitogenic stimulation. Experiments were conducted on health volunteer blood specimens to assess analytical performance characteristics of the assay. Both variance and effect size were assessed in health normal subjects. Results: Analytical performance data shows excellent reproducibility with coefficients of variation less than 20% for most mitogenic conditions. Additional performance metrics like effect of gating parameters and reagent stability were quantified. The effect of pre-analytical variables such as sample handing conditions will be presented as well. Conclusions: The LymPro test, which measures mitogenic response to peripheral blood lymphocytes, is demonstrating suitable analytical performance for use in a fit-for-purpose fashion in the Company’s hands. P3-118
RETROSPECTIVE ANALYSIS OF CLINICAL PROGNOSIS OF SUBJECTS FROM A 2005 STUDY USING THE LYMPRO ASSAY
Gerald Commissiong, Amarantus Bioscience Holdings, Inc., San Francisco, California, United States. Contact e-mail: tiffini.clark@ amarantus.com Background: Initial studies by Thomas Arendt et.al, at the University of Leipzig identified the mitogenic response of peripheral blood lymphocytes (PLB) as a potential biomarker of Alzheimer’s disease (AD)[Stieler, JT, and Arendt, T.; et al. Neuroreport 2001; 12(18):3969-3972]. This finding was confirmed in a second study conducted by AAA, where the authors were able to retrospectively differentiate AD from Other Dementias [(OD), mostly Idiopathic Parkinson’s disease] with 95% sensitivity and 90% specificity [Steiler, J et al, 2012. Neurobio Aging 33:234-341]. Clinical followup of the second cohort of patients was followed up over the past 8 years. Methods: Review of the existing clinical records of the subjects who participated in the Neurobio of Aging study provide an opportunistic cohort of subjects with which to begin to assess the LymPro assay for any potential prognostic utility. In particular, looking at the healthy normal controls and seeing which if any progressed would be of primary interest. Of secondary interest, review of the patients in the AD or PDD groups may provide insight into further development within a disease severity. In particular, biomarker ends points from the 2005 assay were assessed for their ability to correctly predict progression to cognitive impairment or other indications within each of the 3 sub-cohorts of subjects (N¼28 controls, N¼xx, Alzheimer’s disease patients, N¼yy Parkinson disease patients). Logistic regression was used for categorical endpoints whereas proportional-hazard models were used when time-to-event data were available. Results: Review of the 8 years of clinical records of the N¼ 28 control subjects from the original study reveals interesting prognostic information gleaned from the original wet biology biomarkers. In particular, two markers to be presented show hints of prognostic utility with weak statistical significance. Conclusions: Retrospective analysis of the prospective clinical records of participants in the 2005 LymPro study provide an opportunistic look at the prognostic value of the LymPro assay results. Although the sample size is small, individual markers within various lymphocyte subpopulations were assessed as candidate prognostic markers, some with weakly significant results. These results suggest that further evaluation in larger sample sizes is worthwhile. P3-119
STUDY OF DNA METHYLATION OF APP AND APOE GENES IN A SAMPLE OF COLOMBIAN ALZHEIMER’S DISEASE
Hernan G. Hernandez1, Adriana Marcela Mejia1, Maria Fernanda Mahecha1, Rodrigo Pardo1, Gonzalo Arboleda1, Juan Jose Yunis1, Diego Forero2, Humberto Arboleda1, 1UNAL, Bogota,