- Email: [email protected]
Longitudinal volumetric MRI analysis for use in Alzheimer's disease multisite clinical trials: Comparison to analysis methods used in ADNI and correlation to MMSE change
Poster Presentations P3
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amnestic mild cognitive impairment (MCI, n ¼ 27), older adults with informant-verified cognitive complaints but no significant psychometric impairment (CC, n ¼ 16), and healthy elderly controls (HC, n ¼ 25) from two academic medical centers. Assessment included detailed neuropsychological and clinical evaluations and 3T structural MRI scans. Visual contrast sensitivity was assessed separately for both eyes using the FDT-2 (Welch Allyn, Syracuse, NY) in 55 visual field regions. Voxel-based morphometry (VBM) was used to extract grey matter density (GMD) maps. Summary statistics detailing alterations in contrast sensitivity (mean deviation, MD; pattern standard deviation, PSD), 110 threshold measures from 55 retinal regions of each eye, and demographic and cognitive performance variables were compared between groups using ANCOVA, covaried for age at exam, gender, and years of education. The relationships between global GMD, MD, and PSD were assessed using SPM5. Results: Significant differences across groups were detected in FDT-2 measures of overall and local contrast sensitivity, including both MD and PSD, and in 36 right eye retinal regions and 48 left eye retinal regions (p < 0.05 to p < .0001, Figure 1). AD and MCI patients demonstrated the greatest reduction in contrast sensitivity relative to HCs, with CC participants showing an intermediate level of impairment. MD and PSD were significantly related to hippocampal GMD in the left
and bilateral hippocampi, respectively (p < 0.01 (unc.), Figure 2). Conclusions: Contrast sensitivity, as measured by the FDT-2 system, is reduced in patients with AD and MCI and may represent a novel and complementary biomarker for detecting and monitoring AD-related neurodegeneration. P3-225
LONGITUDINAL VOLUMETRIC MRI ANALYSIS FOR USE IN ALZHEIMER’S DISEASE MULTISITE CLINICAL TRIALS: COMPARISON TO ANALYSIS METHODS USED IN ADNI AND CORRELATION TO MMSE CHANGE
Katherine Chong, Wan Chi Lau, Jason Leong, Joyce Suhy, Joonmi Oh, Synarc Inc., San Francisco, CA, USA. Contact e-mail: katherine.chong@ synarc.com Background: The aim of this study was to validate the Synarc in-house analysis methods that quantify cerebral atrophy using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data set. Imaging biomarkers included in this study were whole brain atrophy (WBA), ventricular enlargement (VE) and hippocampus volume (HV) measurement. Methods: A sample of 101 subjects from the ADNI database was used (48 AD, 29 MCI, and 24 normal controls). The WBA, VE and HV were compared to the analysis results from two academic research groups from the same subjects: differential bias correction-brain boundary shift integral (DBC-BBSI) and ventricular-BSI (VBSI) from the Dementia Research Centre (DRC), and cross-sectional FreeSurfer based hippocampus volume (HV-FS) from the Center for Imaging of Neurodegenerative Disease (CIND). Standard least square mean (LSM) tests were used for sub-group comparisons. The standard method to calculate sample sizes that give 80% power and 5% significance level to detect 25% treatment effect were used. Non-parametric Spearman method was used for a correlation test. The results were reported as mean (standard deviation) unless otherwise noted. In this study, p < 0.05 was regarded as significant. Results: The annualized rate changes for WBA (0.9 (1.0) %), VE (7.9 (9.3) %) and HV (3.1 (2.9) %) were statistically equivalent to DBC-BBSI (1.1 (1.0) %, P ¼ 0.107), VBSI (7.7 (7.9) %, P ¼ 0.827), and HV-FS (3.0 (3.7) %, P ¼ 0.844), respectively, for all subjects. The LSMs for WBA (1.4 (0.1) %), VE (10.8 (1.3) %) and HV (4.2 (0.4) %) in AD were significantly higher than in controls (0.2 (0.2) %, 3.5 (1.8) %, 1.5 (0.6) %, respectively). The required sample sizes using WBA, VE and HV were 88, 77 and 143, respectively. Lastly, all imaging biomarkers
S518
Poster Presentations P3
correlated moderately with change in MMSE score. Conclusions: We conclude that WBA, VE and HV rates of change from our institute are not significantly different than those from the DRC and CIND, respectively. We also observed that the measured WBA, VE and HV rate changes were significantly higher in AD subjects relative to the normal control group, showing that our methods were sensitive enough to detect changes in subjects with AD. P3-226
IN VITRO CELLULAR UPTAKE OF A MAGNETIC RESONANCE IMAGING (MRI)/FLUORESCENT CONTRAST AGENT FOR DETECTION OF CATHEPSIN-D ACTIVITY IN ALZHEIMER’S DISEASE
Robert M. Ta1,2, Alex X. Li1, Mojmir Suchy1,3, Robert H. E. Hudson3, Stephen H. Pasternak4,5, Robert Bartha1,2, 1Imaging Research Group, Robarts Research Institute, London, ON, Canada; 2Department of Medical Biophysics, University of Western Ontario, London, ON, Canada; 3 Department of Chemistry, University of Western Ontario, London, ON, Canada; 4Molecular Brain Research Group, Robarts Research Institute, London, ON, Canada; 5Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada. Contact e-mail: rta@ imaging.robarts.ca Background: There are currently no clinically useful biomarkers for the early diagnosis of Alzheimer’s disease (AD). Cathepsin D (CatD) is a lysosomal protease present at elevated levels in amyloid plaques and neuronal cells of AD patients. We have synthesized a magnetic resonance imaging (MRI)/fluorescent contrast agent, DOTA-CAT, to detect CatD. DOTA-CAT consists of a DOTA-caged metal ion, coupled to a cell-penetrating peptide sequence and a CatD recognition site. A fluorescent probe, Oregon Green, was also attached to DOTA-CAT to monitor its uptake optically. The purpose of this study was to establish the cellular uptake of this MRI/fluorescent contrast agent targeting CatD. Methods: SN56 cells, a neuronal cell line, were cultured and differentiated. To simulate conditions of increased CatD, cells were transfected with a plasmid which stimulates high level expression of human CatD tagged with red fluorescent protein. Varying concentrations (5, 10, 50, 100 mM) of DOTA-CAT were added to the media of SN56 cells and confocal microscopy was performed at 30 minutes. Uptake was quantified by counting the proportion of cells which were labeled with DOTA-CAT expressed as Mean 6 SEM. Lastly, cleavage experiments on DOTA-CAT were performed using purified CatD and analyzed using electrospray-ionization mass spectrometry (ESI-MS). Results: In uptake experiments, 19 6 2% of cells exposed to the agent at 5 mM took up DOTA-CAT, and this number increased with concentration such that at 100 mM, 78 6 7% of cells took up DOTA-CAT. In contrast, a maximum of 5 6 1% of cells not over-expressing CatD took up DOTA-CAT over the entire concentration range. DOTA-CAT was observed intracellularly and in intracellular vesicles frequently co-localized with red fluorescent protein tagged-CatD within lysosomes. In cleavage experiments, incubation of DOTA-CAT with CatD produced a 1906.6 Da fragment confirming the cleavage of DOTA-CAT at the predicted CatD recognition sequence. Conclusions: These experiments demonstrate that DOTA-CAT interacts with CatD and is cleaved as predicted. Furthermore, DOTA-CAT is preferentially taken up by SN56 cells over-expressing CatD in a concentration dependant manner. Therefore, DOTA-CAT shows significant potential as a molecular imaging probe that will be further evaluated in future experiments using an in-vivo model of AD. P3-227
PLASMA LEVELS OF HOMOCYSTEINE AND RED CELL FOLATE CORRELATE WITH NEUROLOGICAL COMPOSITE Z-SCORES IN ALZHEIMER’S DISEASE AND HEALTHY SUBJECTS: THE AUSTRALIAN IMAGING BIOMARKER LIFESTYLE (AIBL) STUDY OF AGING
Noel G. Faux1, Kathryn A. Ellis1, Chris J. Fowler1, Ralph Martins2, Kelly K. Pertile1, Christopher Rowe3, Rebecca L. Rumble1, Cassandra Szoeke4, Lorien Porter5, Alan Rembach4, Brett Trounson1, Colin Masters1, David Ames5, Ashley I. Bush1 AIBL Research Group1Mental Health Research Institute, Parkville, Australia; 2School of
Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, Australia; 3University of Melbourne, Austin Health, Heidelberg, Australia; 4CSIRO Molecular and Health Technologies, Parkville, Australia; 5National Ageing Research Institute, Parkville, Australia. Contact e-mail: [email protected] Background: Homocysteine is elevated in Alzheimer’s disease (AD) patients and is negatively correlated with cognitive performance in both AD and healthy controls (HC). We aimed to confirm these finding and investigate if there are associated alterations in the red cell and serum folate and plasma vitamin B12 levels in the large Australian Imaging Biomarker Lifestyle (AIBL) study of Ageing cohort. Methods: We examined the baseline clinical pathology results from the AIBL cohort, which consist of 1112 participants (768 HC, 133 Mild Cognitive Impaired [MCI] patients and 211 AD patients). Univariate analysis was performed using linear modeling to test for any difference in plasma homocysteine, B12, serum folate and red cell folate between the clinical cohorts. Multiple regression with age was used to investigate the correlation of these values with four psychological composite z-scores: short- and long-term episodic memory and, global cognition (GC). Results: Following adjustment for age and gender, we found that plasma homocysteine was significantly (p < 0.01) elevated, and that red cell folate was significantly (p < 0.01) lower in AD patients compared to HC participants. Furthermore, homocysteine is negatively correlated with short- and long- episodic memory composite z-scores (p < 0.01, p ¼ 0.04, short- and long-term episodic memory respectively). Red cell folate is positively correlated with short-term episodic memory composite z-scores (p ¼ 0.012), while longterm episodic memory, and GC composite z-scores showed a quadratic (inverted U) relationship (p ¼ 0.014, p ¼ 0.036, long-term episodic memory, and GC composite z-score respectively). The relationship between homocysteine and both serum and red cell folate was shown to be a quadratic (inverted U) relationship (p ¼ 0.002 and < 0.001, serum and red cell folate respectively) Conclusions: The analysis of one of the largest cohorts studying AD shows clearly that AD patients have elevated levels of plasma homocysteine and decreased levels of red cell folate in comparison to HC and, that homocysteine levels correlate negatively with the neuropsychological composite z-scores regardless of clinical classification, thus corroborating previous research findings in this unique and well characterized cohort. P3-228
DETECTING AMYLOID-BETA OLIGOMERS IN ALZHEIMER PATIENT’S BLOOD USING MULTIMER DETECTION SYSTEM
Seong An1, Kuntaek Lim2, Byungsub Lee2, Gwang Je Kim2, Mino Kang1, Seongmin Kang2, YoungSoon Yang3, Hae Ri Na4, Young Chul Youn5, SangYun Kim6, 1Kyungwon University, Sungnam-si, Republic of Korea; 2 PeopleBio Inc., Seoul, Republic of Korea; 3Department of Neurology, Hyoja Geriatric Hospital, Yongin-si, Republic of Korea; 4Bobath Memorial Hospital, Sungnam-si, Republic of Korea; 5Chung-ang University, College of Medicine, Seoul, Republic of Korea; 6Seoul University School of Medicine, Sungnam-si, Republic of Korea. Contact e-mail: [email protected] Background: The detection of the aggregated or oligomeric forms of various biomarkers in blood and CSF was suggested with possibility of providing robust diagnosis for various progressive neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Prion diseases. Multimer Detection System (MDS) was initially developed for the detection of abnormal prion proteins in blood. In this report, MDS was adapted for Alzheimer’s Disease, targeting Amyloid-beta (Ab) oligomers in blood and CSF. Methods: MDS was a competition assay using capturing antibodies and epitope-overlapping detection antibodies for the detection of only oligomers from monomers in any protein-misfolding diseases. Previously, MDS could differentiate recombinant Ab peptide spiked in plasma and limited CSF samples from patients died of AD in comparison with non-AD controls. In this preliminary experiments, MDS was used to detect Ab oligomers in blood samples from possible AD patients. Results: MDS showed differentiation between AD and non-AD in the preliminary experiments using limited blood samples. Interestingly, CDR1 patient samples showed higher signals than CDR3 AD samples. Conclusions: MDS showed a possibility to differentiate Alzheimer’s patients from non-AD by detecting Ab oligomers in blood.
S517
amnestic mild cognitive impairment (MCI, n ¼ 27), older adults with informant-verified cognitive complaints but no significant psychometric impairment (CC, n ¼ 16), and healthy elderly controls (HC, n ¼ 25) from two academic medical centers. Assessment included detailed neuropsychological and clinical evaluations and 3T structural MRI scans. Visual contrast sensitivity was assessed separately for both eyes using the FDT-2 (Welch Allyn, Syracuse, NY) in 55 visual field regions. Voxel-based morphometry (VBM) was used to extract grey matter density (GMD) maps. Summary statistics detailing alterations in contrast sensitivity (mean deviation, MD; pattern standard deviation, PSD), 110 threshold measures from 55 retinal regions of each eye, and demographic and cognitive performance variables were compared between groups using ANCOVA, covaried for age at exam, gender, and years of education. The relationships between global GMD, MD, and PSD were assessed using SPM5. Results: Significant differences across groups were detected in FDT-2 measures of overall and local contrast sensitivity, including both MD and PSD, and in 36 right eye retinal regions and 48 left eye retinal regions (p < 0.05 to p < .0001, Figure 1). AD and MCI patients demonstrated the greatest reduction in contrast sensitivity relative to HCs, with CC participants showing an intermediate level of impairment. MD and PSD were significantly related to hippocampal GMD in the left
and bilateral hippocampi, respectively (p < 0.01 (unc.), Figure 2). Conclusions: Contrast sensitivity, as measured by the FDT-2 system, is reduced in patients with AD and MCI and may represent a novel and complementary biomarker for detecting and monitoring AD-related neurodegeneration. P3-225
LONGITUDINAL VOLUMETRIC MRI ANALYSIS FOR USE IN ALZHEIMER’S DISEASE MULTISITE CLINICAL TRIALS: COMPARISON TO ANALYSIS METHODS USED IN ADNI AND CORRELATION TO MMSE CHANGE
Katherine Chong, Wan Chi Lau, Jason Leong, Joyce Suhy, Joonmi Oh, Synarc Inc., San Francisco, CA, USA. Contact e-mail: katherine.chong@ synarc.com Background: The aim of this study was to validate the Synarc in-house analysis methods that quantify cerebral atrophy using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data set. Imaging biomarkers included in this study were whole brain atrophy (WBA), ventricular enlargement (VE) and hippocampus volume (HV) measurement. Methods: A sample of 101 subjects from the ADNI database was used (48 AD, 29 MCI, and 24 normal controls). The WBA, VE and HV were compared to the analysis results from two academic research groups from the same subjects: differential bias correction-brain boundary shift integral (DBC-BBSI) and ventricular-BSI (VBSI) from the Dementia Research Centre (DRC), and cross-sectional FreeSurfer based hippocampus volume (HV-FS) from the Center for Imaging of Neurodegenerative Disease (CIND). Standard least square mean (LSM) tests were used for sub-group comparisons. The standard method to calculate sample sizes that give 80% power and 5% significance level to detect 25% treatment effect were used. Non-parametric Spearman method was used for a correlation test. The results were reported as mean (standard deviation) unless otherwise noted. In this study, p < 0.05 was regarded as significant. Results: The annualized rate changes for WBA (0.9 (1.0) %), VE (7.9 (9.3) %) and HV (3.1 (2.9) %) were statistically equivalent to DBC-BBSI (1.1 (1.0) %, P ¼ 0.107), VBSI (7.7 (7.9) %, P ¼ 0.827), and HV-FS (3.0 (3.7) %, P ¼ 0.844), respectively, for all subjects. The LSMs for WBA (1.4 (0.1) %), VE (10.8 (1.3) %) and HV (4.2 (0.4) %) in AD were significantly higher than in controls (0.2 (0.2) %, 3.5 (1.8) %, 1.5 (0.6) %, respectively). The required sample sizes using WBA, VE and HV were 88, 77 and 143, respectively. Lastly, all imaging biomarkers
S518
Poster Presentations P3
correlated moderately with change in MMSE score. Conclusions: We conclude that WBA, VE and HV rates of change from our institute are not significantly different than those from the DRC and CIND, respectively. We also observed that the measured WBA, VE and HV rate changes were significantly higher in AD subjects relative to the normal control group, showing that our methods were sensitive enough to detect changes in subjects with AD. P3-226
IN VITRO CELLULAR UPTAKE OF A MAGNETIC RESONANCE IMAGING (MRI)/FLUORESCENT CONTRAST AGENT FOR DETECTION OF CATHEPSIN-D ACTIVITY IN ALZHEIMER’S DISEASE
Robert M. Ta1,2, Alex X. Li1, Mojmir Suchy1,3, Robert H. E. Hudson3, Stephen H. Pasternak4,5, Robert Bartha1,2, 1Imaging Research Group, Robarts Research Institute, London, ON, Canada; 2Department of Medical Biophysics, University of Western Ontario, London, ON, Canada; 3 Department of Chemistry, University of Western Ontario, London, ON, Canada; 4Molecular Brain Research Group, Robarts Research Institute, London, ON, Canada; 5Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada. Contact e-mail: rta@ imaging.robarts.ca Background: There are currently no clinically useful biomarkers for the early diagnosis of Alzheimer’s disease (AD). Cathepsin D (CatD) is a lysosomal protease present at elevated levels in amyloid plaques and neuronal cells of AD patients. We have synthesized a magnetic resonance imaging (MRI)/fluorescent contrast agent, DOTA-CAT, to detect CatD. DOTA-CAT consists of a DOTA-caged metal ion, coupled to a cell-penetrating peptide sequence and a CatD recognition site. A fluorescent probe, Oregon Green, was also attached to DOTA-CAT to monitor its uptake optically. The purpose of this study was to establish the cellular uptake of this MRI/fluorescent contrast agent targeting CatD. Methods: SN56 cells, a neuronal cell line, were cultured and differentiated. To simulate conditions of increased CatD, cells were transfected with a plasmid which stimulates high level expression of human CatD tagged with red fluorescent protein. Varying concentrations (5, 10, 50, 100 mM) of DOTA-CAT were added to the media of SN56 cells and confocal microscopy was performed at 30 minutes. Uptake was quantified by counting the proportion of cells which were labeled with DOTA-CAT expressed as Mean 6 SEM. Lastly, cleavage experiments on DOTA-CAT were performed using purified CatD and analyzed using electrospray-ionization mass spectrometry (ESI-MS). Results: In uptake experiments, 19 6 2% of cells exposed to the agent at 5 mM took up DOTA-CAT, and this number increased with concentration such that at 100 mM, 78 6 7% of cells took up DOTA-CAT. In contrast, a maximum of 5 6 1% of cells not over-expressing CatD took up DOTA-CAT over the entire concentration range. DOTA-CAT was observed intracellularly and in intracellular vesicles frequently co-localized with red fluorescent protein tagged-CatD within lysosomes. In cleavage experiments, incubation of DOTA-CAT with CatD produced a 1906.6 Da fragment confirming the cleavage of DOTA-CAT at the predicted CatD recognition sequence. Conclusions: These experiments demonstrate that DOTA-CAT interacts with CatD and is cleaved as predicted. Furthermore, DOTA-CAT is preferentially taken up by SN56 cells over-expressing CatD in a concentration dependant manner. Therefore, DOTA-CAT shows significant potential as a molecular imaging probe that will be further evaluated in future experiments using an in-vivo model of AD. P3-227
PLASMA LEVELS OF HOMOCYSTEINE AND RED CELL FOLATE CORRELATE WITH NEUROLOGICAL COMPOSITE Z-SCORES IN ALZHEIMER’S DISEASE AND HEALTHY SUBJECTS: THE AUSTRALIAN IMAGING BIOMARKER LIFESTYLE (AIBL) STUDY OF AGING
Noel G. Faux1, Kathryn A. Ellis1, Chris J. Fowler1, Ralph Martins2, Kelly K. Pertile1, Christopher Rowe3, Rebecca L. Rumble1, Cassandra Szoeke4, Lorien Porter5, Alan Rembach4, Brett Trounson1, Colin Masters1, David Ames5, Ashley I. Bush1 AIBL Research Group1Mental Health Research Institute, Parkville, Australia; 2School of
Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, Australia; 3University of Melbourne, Austin Health, Heidelberg, Australia; 4CSIRO Molecular and Health Technologies, Parkville, Australia; 5National Ageing Research Institute, Parkville, Australia. Contact e-mail: [email protected] Background: Homocysteine is elevated in Alzheimer’s disease (AD) patients and is negatively correlated with cognitive performance in both AD and healthy controls (HC). We aimed to confirm these finding and investigate if there are associated alterations in the red cell and serum folate and plasma vitamin B12 levels in the large Australian Imaging Biomarker Lifestyle (AIBL) study of Ageing cohort. Methods: We examined the baseline clinical pathology results from the AIBL cohort, which consist of 1112 participants (768 HC, 133 Mild Cognitive Impaired [MCI] patients and 211 AD patients). Univariate analysis was performed using linear modeling to test for any difference in plasma homocysteine, B12, serum folate and red cell folate between the clinical cohorts. Multiple regression with age was used to investigate the correlation of these values with four psychological composite z-scores: short- and long-term episodic memory and, global cognition (GC). Results: Following adjustment for age and gender, we found that plasma homocysteine was significantly (p < 0.01) elevated, and that red cell folate was significantly (p < 0.01) lower in AD patients compared to HC participants. Furthermore, homocysteine is negatively correlated with short- and long- episodic memory composite z-scores (p < 0.01, p ¼ 0.04, short- and long-term episodic memory respectively). Red cell folate is positively correlated with short-term episodic memory composite z-scores (p ¼ 0.012), while longterm episodic memory, and GC composite z-scores showed a quadratic (inverted U) relationship (p ¼ 0.014, p ¼ 0.036, long-term episodic memory, and GC composite z-score respectively). The relationship between homocysteine and both serum and red cell folate was shown to be a quadratic (inverted U) relationship (p ¼ 0.002 and < 0.001, serum and red cell folate respectively) Conclusions: The analysis of one of the largest cohorts studying AD shows clearly that AD patients have elevated levels of plasma homocysteine and decreased levels of red cell folate in comparison to HC and, that homocysteine levels correlate negatively with the neuropsychological composite z-scores regardless of clinical classification, thus corroborating previous research findings in this unique and well characterized cohort. P3-228
DETECTING AMYLOID-BETA OLIGOMERS IN ALZHEIMER PATIENT’S BLOOD USING MULTIMER DETECTION SYSTEM
Seong An1, Kuntaek Lim2, Byungsub Lee2, Gwang Je Kim2, Mino Kang1, Seongmin Kang2, YoungSoon Yang3, Hae Ri Na4, Young Chul Youn5, SangYun Kim6, 1Kyungwon University, Sungnam-si, Republic of Korea; 2 PeopleBio Inc., Seoul, Republic of Korea; 3Department of Neurology, Hyoja Geriatric Hospital, Yongin-si, Republic of Korea; 4Bobath Memorial Hospital, Sungnam-si, Republic of Korea; 5Chung-ang University, College of Medicine, Seoul, Republic of Korea; 6Seoul University School of Medicine, Sungnam-si, Republic of Korea. Contact e-mail: [email protected] Background: The detection of the aggregated or oligomeric forms of various biomarkers in blood and CSF was suggested with possibility of providing robust diagnosis for various progressive neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Prion diseases. Multimer Detection System (MDS) was initially developed for the detection of abnormal prion proteins in blood. In this report, MDS was adapted for Alzheimer’s Disease, targeting Amyloid-beta (Ab) oligomers in blood and CSF. Methods: MDS was a competition assay using capturing antibodies and epitope-overlapping detection antibodies for the detection of only oligomers from monomers in any protein-misfolding diseases. Previously, MDS could differentiate recombinant Ab peptide spiked in plasma and limited CSF samples from patients died of AD in comparison with non-AD controls. In this preliminary experiments, MDS was used to detect Ab oligomers in blood samples from possible AD patients. Results: MDS showed differentiation between AD and non-AD in the preliminary experiments using limited blood samples. Interestingly, CDR1 patient samples showed higher signals than CDR3 AD samples. Conclusions: MDS showed a possibility to differentiate Alzheimer’s patients from non-AD by detecting Ab oligomers in blood.