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Sphingomyelin is elevated in cerebrospinal fluid of Alzheimer's disease patients
S140
POSTER PRESENTATION P1
Aß was detected also at the surfaces of the respiratory epithelium in the middle meatus and ventral meatus. The control sections showed no Aß immunopositive staining. Conclusions: The present study demonstrated Aß imunoreactivity in the olfactory epithelium and respiratory epithelium of nasal tissue from Tg2576 mice. Aß-positive dots were mainly observed in the basal cell layer of the olfactory epithelium and the sub-epithelial region of the dorsal meatus. This observation is in good agreement with a previous report in humans (Arnold et al., 2010). The olfactory epithelium has relatively easy accessibility compared with the brain, and thus could therefore provide a useful source of biomarkers for the diagnosis of AD.
(w37.5-38.5) The most intense signal corresponded to PC species followed by SM, PI and PE with ratios to PC intensity of approximately 0.3, 0.15 and 0.1, respectively. Five PE, six PC, six PI and eight SM species have been detected with average relative standard deviation of 16%, 3%, 6% and 8% respectively. Our pilot study showed statistically significant increase of SM levels (24.3% 6 2.4%) in the CSF of probable AD individuals vs. controls. Conclusions: Our findings indicate that sphingomyelin levels in the CSF could potentially provide a new lead in AD biomarker research as well as in elucidating the role of SM in AD pathogenesis. P1-094
P1-092
THE EFFECT OF FORMIC ACID TREATMENT ON AGGREGATED Ab
Masahiro Koge1, Ikuo Tooyama2, Naoko Kameshima1, Takaomi Fukuhara1, Toshifumi Nanjo1, 1Panasonic Healthcare Co., Ltd., Toon, Ehime; 2Shiga University of Medical Science, Shiga. Background: ß-amyloid peptides (Aß) are major players in the pathology of Alzheimer’s disease (AD), and have been the subject of close attention recently as potential biomarkers for the diagnosis of AD. Aß readily aggregate (aggAß), especially Aß42, making them more difficult to measure precisely. This study thus investigated the effect of formic acid (FA) treatment on agg-Aß to improve assay ability. Methods: We analyzed the effect of FA treatment of agg-Aß by PAGE (tested samples were Monomer Aß (Aß1-42, Peptide Institute) and agg-Aß) and ELISA (tested samples were Monomer Aß, agg-Aß, and human samples). Monomer Aß was incubated in the same way as aggAß. FA was added directly to each sample to a concentration of at least 70%, and the sample was neutralized before assaying. Molecular weights and Aß concentrations with and without FA treatment were measured. Human samples were nasal mucosa collected by the swab. ELISA kits containing antibodies with varying sites of recognition (anti-human Aß1-42, Aß1-x, Aßx42, Agg-Aß, Oligomer Aß) were used. Results: PAGE analysis revealed a higher molecular weight for untreated agg-Aß than for monomer Aß. Following treatment with FA, the molecular weight of agg-Aß decreased. ELISA showed stronger signals in agg-Aß and human samples following FA treatment compared to untreated samples without FA when we used ELISA kits for Aß1-42, Aß1-x, Aßx-42. Whereas, they were weak signals when we used ELISA kit for Agg-Aß, Oligomer Aß. Conclusions: Our results indicated that FA treatment has the potential of degrading and solubilizing aggAß. In addition, Aß exists as agg-Aß in human nasal cavity. P1-093
SPHINGOMYELIN IS ELEVATED IN CEREBROSPINAL FLUID OF ALZHEIMER’S DISEASE PATIENTS
Marko Kosicek1, Silva Katusic Hecimovic2, Stephan Kirsch3, Raphael Bene4, Zlatko Trkanjec5, Marina Titlic6, Laura Bindila3, Jasna Peter-Katalinic3, 1Rudjer Boskovic Institute, Zagreb; 2Rudjer Boskovic Institute, Zagreb; 3Institute of Medical Physics and Biophysics, M€ unster; 4University Hospital Sestre milosrdnice, Zagreb; 5University Hospital Sestre milosrdnice, Zagreb; 6University Hospital Split, Split. Background: Lipid alterations in Alzheimer’s disease (AD) brains have been reported. However, only few of them focused on lipid changes in the cerebrospinal fluid (CSF), which is the most informative fluid source for neurodegenerative disease prognosis and diagnosis, due to its constant physical contact with the brain. Although phospholipids levels in the CSF are low, developments in mass spectrometry (MS) have enabled fast and sensitive detection of lipid species even in complex biological matrixes. Methods: We developed an on-line HPLC/MS method for phospholipid profiling in the CSF based on nano-HPLC separation using Amide column and detection with electrospray (ESI) quadrupole - time of flight (QTOF) MS. We achieved good separation, reproducibility and sensitivity for monitoring major phospholipid classes in the CSF: phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI) and sphingomyelin (SM). To elucidate phospholipid changes in the CSF, a pilot study was performed on CSF samples (N ¼ 16) from individuals with probable AD and non-demented controls. Results: The HPLC elution order of each phospholipid classes in CSF was: PE (w33.5-35.0 min), PC (w34.5-35.5 min), PI (w36.0-37.0 min) and SM
VITAMIN D IN ELDERLY PSYCHIATRIC INPATIENTS
Maria I. Lapid, Matthew Drake, Jennifer Geske, Simon Kung, Mark Frye, Mayo Clinic, Rochester, Minnesota. Background: The purpose ofthis study was to investigate the vitamin D status of psychogeriatric inpatients and explore whether any associations exist between depression, dementia and other psychiatric diagnoses and vitamin D levels. Methods: A descriptive, retrospective chart review ofpsychiatric inpatients age 65 years and older who had vitamin D levels drawn within one week of admission was conducted. Demographic and clinical information were collected. Analysis ofvariance was used to test for a difference in vitamin D levels by season. Correlation ofMMSE with vitamin D levels was tested using Spearman rankorder correlation. The association ofvitamin D levels with psychiatric diagnoses was examined using univariate logistic regression models, and ofvitamin D deficiency status with psychiatric diagnoses using Fisher’s exact test. Results: Data from 141 subjects were included. Mean age was 77.78 years, range 65-99 . Subjects were 61% females and predominantly (96%) Caucasian. The most frequent discharge diagnoses were major depressive disorder (57%) and dementia (27%), with delirium (9%), anxiety (8.5%) , and bipolar disorder (8%) less frequent. One-third of all subjects had more than one diagnosis. Mean Mini Mental Status Examination (MMSE) score was 24, range 3-30. Based on total serum 25-hydroxyvitamin D [25(OH)D] levels, 92 (65%) had vitamin D levels within the optimal range, while 43 (30.4%) showed mild to moderate (10-24 ng/mL) and 6 (4.2%) severe <<10 ng/ mL) vitamin D deficiency. There were no differences in mean vitamin D levels by season. No correlations were found between MMSE scores and vitamin D levels. There were no significant associations between psychiatric diagnoses and vitamin D levels, whether optimal or deficient. Conclusions: Vitamin D deficiency was present in one-third ofthe study group. There was no seasonal variation in vitamin D levels. No associations were found between vitamin D levels and psychiatric diagnoses or global cognitive function. Despite the lack of association, vitamin D deficiency is a common problem and further studies are needed to identify and treat psychogeriatric patients who are affected and may potentially benefit from treatment. P1-095
STEM CELL FACTOR PLASMA LEVELS PREDICT COGNITIVE DECLINE IN ALZHEIMER’S DISEASE PATIENTS
Christoph Laske1, Elke Stransky2, Andreas Fallgatter2, Thomas Leyhe2, 1 Department of Psychiatry, T€ubingen; 2Department of Psychiatry and Psychotherapy, Tuebingen. Background: Alzheimer’s disease (AD) is the most common cause of cognitive decline in the elderly and is characterized by massive neuronal cell loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor (HGF) that promotes neuroprotective effects and supports neurogenesis in the brain. Decreased SCF plasma levels have been described in AD patients. Whether SCF plasma levels are also associated with the rate of cognitive decline in AD patients is poorly understood so far. Methods: Forty AD outpatients from the memory clinic at the University Hospital of Psychiatry and Psychotherapy T€ubingen were included in the study. All the patients were followed up prospectively and were re-examined clinically 1 year later (range 11-13 months). Among AD patients, 28 patients showed a slow cognitive decline (decrease of MMSE score ¼ 4/year) and 12 patients displayed a fast cognitive decline (decrease of MMSE score > 4/year). Soluble SCF plasma levels were measured by ELISA. Results: In the present study we demonstrate that SCF plasma levels are significantly decreased in AD
POSTER PRESENTATION P1
Aß was detected also at the surfaces of the respiratory epithelium in the middle meatus and ventral meatus. The control sections showed no Aß immunopositive staining. Conclusions: The present study demonstrated Aß imunoreactivity in the olfactory epithelium and respiratory epithelium of nasal tissue from Tg2576 mice. Aß-positive dots were mainly observed in the basal cell layer of the olfactory epithelium and the sub-epithelial region of the dorsal meatus. This observation is in good agreement with a previous report in humans (Arnold et al., 2010). The olfactory epithelium has relatively easy accessibility compared with the brain, and thus could therefore provide a useful source of biomarkers for the diagnosis of AD.
(w37.5-38.5) The most intense signal corresponded to PC species followed by SM, PI and PE with ratios to PC intensity of approximately 0.3, 0.15 and 0.1, respectively. Five PE, six PC, six PI and eight SM species have been detected with average relative standard deviation of 16%, 3%, 6% and 8% respectively. Our pilot study showed statistically significant increase of SM levels (24.3% 6 2.4%) in the CSF of probable AD individuals vs. controls. Conclusions: Our findings indicate that sphingomyelin levels in the CSF could potentially provide a new lead in AD biomarker research as well as in elucidating the role of SM in AD pathogenesis. P1-094
P1-092
THE EFFECT OF FORMIC ACID TREATMENT ON AGGREGATED Ab
Masahiro Koge1, Ikuo Tooyama2, Naoko Kameshima1, Takaomi Fukuhara1, Toshifumi Nanjo1, 1Panasonic Healthcare Co., Ltd., Toon, Ehime; 2Shiga University of Medical Science, Shiga. Background: ß-amyloid peptides (Aß) are major players in the pathology of Alzheimer’s disease (AD), and have been the subject of close attention recently as potential biomarkers for the diagnosis of AD. Aß readily aggregate (aggAß), especially Aß42, making them more difficult to measure precisely. This study thus investigated the effect of formic acid (FA) treatment on agg-Aß to improve assay ability. Methods: We analyzed the effect of FA treatment of agg-Aß by PAGE (tested samples were Monomer Aß (Aß1-42, Peptide Institute) and agg-Aß) and ELISA (tested samples were Monomer Aß, agg-Aß, and human samples). Monomer Aß was incubated in the same way as aggAß. FA was added directly to each sample to a concentration of at least 70%, and the sample was neutralized before assaying. Molecular weights and Aß concentrations with and without FA treatment were measured. Human samples were nasal mucosa collected by the swab. ELISA kits containing antibodies with varying sites of recognition (anti-human Aß1-42, Aß1-x, Aßx42, Agg-Aß, Oligomer Aß) were used. Results: PAGE analysis revealed a higher molecular weight for untreated agg-Aß than for monomer Aß. Following treatment with FA, the molecular weight of agg-Aß decreased. ELISA showed stronger signals in agg-Aß and human samples following FA treatment compared to untreated samples without FA when we used ELISA kits for Aß1-42, Aß1-x, Aßx-42. Whereas, they were weak signals when we used ELISA kit for Agg-Aß, Oligomer Aß. Conclusions: Our results indicated that FA treatment has the potential of degrading and solubilizing aggAß. In addition, Aß exists as agg-Aß in human nasal cavity. P1-093
SPHINGOMYELIN IS ELEVATED IN CEREBROSPINAL FLUID OF ALZHEIMER’S DISEASE PATIENTS
Marko Kosicek1, Silva Katusic Hecimovic2, Stephan Kirsch3, Raphael Bene4, Zlatko Trkanjec5, Marina Titlic6, Laura Bindila3, Jasna Peter-Katalinic3, 1Rudjer Boskovic Institute, Zagreb; 2Rudjer Boskovic Institute, Zagreb; 3Institute of Medical Physics and Biophysics, M€ unster; 4University Hospital Sestre milosrdnice, Zagreb; 5University Hospital Sestre milosrdnice, Zagreb; 6University Hospital Split, Split. Background: Lipid alterations in Alzheimer’s disease (AD) brains have been reported. However, only few of them focused on lipid changes in the cerebrospinal fluid (CSF), which is the most informative fluid source for neurodegenerative disease prognosis and diagnosis, due to its constant physical contact with the brain. Although phospholipids levels in the CSF are low, developments in mass spectrometry (MS) have enabled fast and sensitive detection of lipid species even in complex biological matrixes. Methods: We developed an on-line HPLC/MS method for phospholipid profiling in the CSF based on nano-HPLC separation using Amide column and detection with electrospray (ESI) quadrupole - time of flight (QTOF) MS. We achieved good separation, reproducibility and sensitivity for monitoring major phospholipid classes in the CSF: phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI) and sphingomyelin (SM). To elucidate phospholipid changes in the CSF, a pilot study was performed on CSF samples (N ¼ 16) from individuals with probable AD and non-demented controls. Results: The HPLC elution order of each phospholipid classes in CSF was: PE (w33.5-35.0 min), PC (w34.5-35.5 min), PI (w36.0-37.0 min) and SM
VITAMIN D IN ELDERLY PSYCHIATRIC INPATIENTS
Maria I. Lapid, Matthew Drake, Jennifer Geske, Simon Kung, Mark Frye, Mayo Clinic, Rochester, Minnesota. Background: The purpose ofthis study was to investigate the vitamin D status of psychogeriatric inpatients and explore whether any associations exist between depression, dementia and other psychiatric diagnoses and vitamin D levels. Methods: A descriptive, retrospective chart review ofpsychiatric inpatients age 65 years and older who had vitamin D levels drawn within one week of admission was conducted. Demographic and clinical information were collected. Analysis ofvariance was used to test for a difference in vitamin D levels by season. Correlation ofMMSE with vitamin D levels was tested using Spearman rankorder correlation. The association ofvitamin D levels with psychiatric diagnoses was examined using univariate logistic regression models, and ofvitamin D deficiency status with psychiatric diagnoses using Fisher’s exact test. Results: Data from 141 subjects were included. Mean age was 77.78 years, range 65-99 . Subjects were 61% females and predominantly (96%) Caucasian. The most frequent discharge diagnoses were major depressive disorder (57%) and dementia (27%), with delirium (9%), anxiety (8.5%) , and bipolar disorder (8%) less frequent. One-third of all subjects had more than one diagnosis. Mean Mini Mental Status Examination (MMSE) score was 24, range 3-30. Based on total serum 25-hydroxyvitamin D [25(OH)D] levels, 92 (65%) had vitamin D levels within the optimal range, while 43 (30.4%) showed mild to moderate (10-24 ng/mL) and 6 (4.2%) severe <<10 ng/ mL) vitamin D deficiency. There were no differences in mean vitamin D levels by season. No correlations were found between MMSE scores and vitamin D levels. There were no significant associations between psychiatric diagnoses and vitamin D levels, whether optimal or deficient. Conclusions: Vitamin D deficiency was present in one-third ofthe study group. There was no seasonal variation in vitamin D levels. No associations were found between vitamin D levels and psychiatric diagnoses or global cognitive function. Despite the lack of association, vitamin D deficiency is a common problem and further studies are needed to identify and treat psychogeriatric patients who are affected and may potentially benefit from treatment. P1-095
STEM CELL FACTOR PLASMA LEVELS PREDICT COGNITIVE DECLINE IN ALZHEIMER’S DISEASE PATIENTS
Christoph Laske1, Elke Stransky2, Andreas Fallgatter2, Thomas Leyhe2, 1 Department of Psychiatry, T€ubingen; 2Department of Psychiatry and Psychotherapy, Tuebingen. Background: Alzheimer’s disease (AD) is the most common cause of cognitive decline in the elderly and is characterized by massive neuronal cell loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor (HGF) that promotes neuroprotective effects and supports neurogenesis in the brain. Decreased SCF plasma levels have been described in AD patients. Whether SCF plasma levels are also associated with the rate of cognitive decline in AD patients is poorly understood so far. Methods: Forty AD outpatients from the memory clinic at the University Hospital of Psychiatry and Psychotherapy T€ubingen were included in the study. All the patients were followed up prospectively and were re-examined clinically 1 year later (range 11-13 months). Among AD patients, 28 patients showed a slow cognitive decline (decrease of MMSE score ¼ 4/year) and 12 patients displayed a fast cognitive decline (decrease of MMSE score > 4/year). Soluble SCF plasma levels were measured by ELISA. Results: In the present study we demonstrate that SCF plasma levels are significantly decreased in AD