- Email: [email protected]
Neprilysin activity in CSF is associated with CSF tau but neither with cerebral amyloid load nor CSF amyloid 1-42 in Alzheimer's disease
Poster Presentations: P4 Table 1 Age Effect Age range (years)
P859
Albumin (mg/ml)
IgG (mg/ml)
Aß1-42 (pg/ml)
Aß1-40 (pg/ml)
Ratio Aß1-42/Aß1-40
35,52 6 5,40 36,63 6 5,58 ns
8,62 6 2,04 8,74 6 2,58 ns
25,30 6 3,46 23,45 6 3,93 0,008
100,20 6 21,58 98,38 6 24,62 ns
0,26 6 0,05 0,25 6 0,06 ns
Aß1-42 (pg/ml)
Aß1-40 (pg/ml)
Ratio Aß1-42/Aß1-40
FTD ( 6 SD) 38,07 6 5,86 9,79 6 3,23 RD ( 6 SD) 34.08 6 4.31 7,91 6 2,35 p value <0,0001 0,0002 FTD: first time donors; RD: repeated donors; ns: not significant.
24,19 6 3,63 24,57 6 3,98 ns
95,10 6 22,03 103,37 6 23,45 0,047
0,27 6 0,06 0,24 6 0,05 0,020
Background: Plasmapheresis has been used in clinical setting to remove proteins in autoimmune diseases, but is also used to collect plasma from healthy individuals who donate plasma to be used for the manufacture of plasma derived therapeutic proteins. However, the impact of plasmapheresis on plasmatic Ab levels after repeated donations has not been studied. The purpose of this study is to evaluate plasmatic Ab levels of individuals undergoing plasmapheresis. Results: No major age effects were seen in any of the studied proteins. The Ab 1-42 detectable by xMAP technology appeared to be slightly lower in older donors (Table 1). The results obtained according to donation frequency are presented in table 2. The albumin and IgG content slightly decreased with repeated donations, with no alteration on the donors’ health status. The results of A b content, detectable by xMAP technology, showed no differences or marginal differences (data widely overlapped) when comparing both groups. Conclusions: A slight decrease of albumin and IgG content in repeated donors, as previously known, is confirmed. No major effects on Ab content in correlation to donation frequency could be observed.
Games-Howell post-hoc tests were computed to test for differences between 4 groups of subjects: subjects with consistent CSF and conversion data (both showing pathological, or non-pathological findings), and subjects with discrepant findings (pathological CSF findings but no conversion at follow-up, or vice versa). Results: Of the 389 subjects with complete data sets as to CSF biomarkers and conversion to AD, 121 (31.1%) had discrepant findings between these two outcome measures: While only 7.1% of the subjects with non-pathological CSF findings converted to AD within the 3-year follow-up time, 75.2% did not convert to AD, although they had the AD-typical CSF pathology. Analyses showed that the 4 subject groups were characterised as follows: Subjects with pathological CSF markers who didn’t convert in the 3-year follow-up time were significantly more impaired in the episodic memory tests (word list delayed recall and recognition, p¼<.0001, and .002, respectively), and in the ideational praxis (p¼.013), compared to non-converters with normal CSF findings. MCI subjects with pathological CSF findings and short-term conversion to AD were characterised by a particularly impaired language performance, compared to non-converters with positive or negative CSF findings (p¼.022, and .033, respectively). Conclusions: To predict short-term conversion to AD in subjects with MCI, a characteristic cognitive profile can help improve the predictive validity of CSF findings.
18-28 ( 6 SD) 50-69 ( 6 SD) p value ns: not significant. Table 2 Donation Frequency Effect Donation frequency
P4-347
Albumin (mg/ml)
IgG (mg/ml)
WHICH MCI SUBTYPES CONVERT TO ALZHEIMER’S DISEASE IN SPITE OF NEGATIVE CSF FINDINGS?
Marinella Damian1, Wolfgang Maier2, Christian Luckhaus3, Johannes Kornhuber4, Johannes Pantel5, Michael H€ull6, Holger Jahn7, Johannes Schr€ oder8, Hermann-Josef Gertz9, Harald Hampel10, Alexander Kurz11, Michael Wagner12, Lucrezia Hausner1, Oliver Peters13, Lutz Froelich14, 1Central Institute of Mental Health, Mannheim, Germany; 2 University of Bonn, Bonn, Germany; 3University D€usseldorf, D€usseldorf, Germany; 4University of Erlangen-N€urnberg, Erlangen, Germany; 5 Institute of General Practice, Goethe University Frankfurt, Frankfurt, Germany; 6University of Freiburg ZGGF, Freiburg, Germany; 7University of Hamburg Medical Center, Hamburg, Germany; 8Psychiatrische Universit€ atsklinik Heidelberg, Heidelberg, Germany; 9Klinik und Poliklinik f€ ur Psychiatrie der Universit€at Leipzig, Leipzig, Germany; 10University of Frankfurt, Frankfurt/Main, Germany; 11Technische Universit€at M€unchen, M€ unchen, Germany; 12German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; 13Charite-Universit€atsmedizin Berlin, Berlin, Germany; 14CIMH Mannheim, Mannheim, Germany. Contact e-mail: [email protected] Background: AD-typical CSF biomarker profiles are often used to predict conversion to AD from mild cognitive impairment (MCI). However, in some MCI subjects, a pathological CSF profile is not as predictive as in others. The aim of this study was to identify the neuropsychological characteristics predicting short-term conversion to AD in spite of negative CSF findings, and no short-term conversion in spite of an AD-typical pathology. Methods: N¼625 subjects were recruited from 13 memory clinics involved in the German Competence Study and followed for up to 3 years. Outcome measures included cognitive variables (e.g. ADAS-cog subtests), conversion to AD, and biological markers (e.g. CSF biomarkers). ANOVAs followed by
P4-348
NEPRILYSIN ACTIVITY IN CSF IS ASSOCIATED WITH CSF TAU BUT NEITHER WITH CEREBRAL AMYLOID LOAD NOR CSF AMYLOID 1-42 IN ALZHEIMER’S DISEASE
Timo Grimmer1, Oliver Goldhardt1, Stefan F€orster2, Alexander Drzezga3, Hans F€orstl4, Alexander Kurz5, Scott Miners6, 1Technische Universit€at M€unchen, Munich, Germany; 2TU Munich, Munich, Germany; 3University of Cologne, Cologne, Germany; 4Technische Universitaet Muenchen, Munich, Germany; 5Technische Universit€at M€unchen, M€unchen, Germany; 6 University of Bristol, Bristol, United Kingdom. Contact e-mail: t. [email protected] Background: Impaired amyloid clearance is a proposed cause of amyloid deposition in sporadic late-onset Alzheimer’s disease (AD). The enzyme Neprilysin is proposed to be primarily responsible for degrading beta-amyloid (A b) in the brain. We aimed to elucidate the role of Neprilysin on invivo brain amyloid load of AD patients using amyloid PET with [11C]PiB and on beta-amyloid1-42 (Ab42) in cerebrospinal fluid (CSF). Methods: Associations between the activity of Neprilysin in CSF, global and regional amyloid load, and concentrations of CSF A b42 and CSF Tau were calculated using linear regression analyses and voxel based analyses with statistical parametric mapping (SPM8), respectively, in 24 AD patients. Results: Neprilysin activity in CSF was not significantly associated with global or regional brain amyloid or CSF A b42 but with CSF Tau (r¼ 0.57, p¼0.004). Conclusions: Impaired amyloid degradation in the brain does not appear to be a major cause of amyloid deposition in sporadic late-onset AD. NEP activity in CSF may be suitable as a marker of neurodegeneration.
P859
Albumin (mg/ml)
IgG (mg/ml)
Aß1-42 (pg/ml)
Aß1-40 (pg/ml)
Ratio Aß1-42/Aß1-40
35,52 6 5,40 36,63 6 5,58 ns
8,62 6 2,04 8,74 6 2,58 ns
25,30 6 3,46 23,45 6 3,93 0,008
100,20 6 21,58 98,38 6 24,62 ns
0,26 6 0,05 0,25 6 0,06 ns
Aß1-42 (pg/ml)
Aß1-40 (pg/ml)
Ratio Aß1-42/Aß1-40
FTD ( 6 SD) 38,07 6 5,86 9,79 6 3,23 RD ( 6 SD) 34.08 6 4.31 7,91 6 2,35 p value <0,0001 0,0002 FTD: first time donors; RD: repeated donors; ns: not significant.
24,19 6 3,63 24,57 6 3,98 ns
95,10 6 22,03 103,37 6 23,45 0,047
0,27 6 0,06 0,24 6 0,05 0,020
Background: Plasmapheresis has been used in clinical setting to remove proteins in autoimmune diseases, but is also used to collect plasma from healthy individuals who donate plasma to be used for the manufacture of plasma derived therapeutic proteins. However, the impact of plasmapheresis on plasmatic Ab levels after repeated donations has not been studied. The purpose of this study is to evaluate plasmatic Ab levels of individuals undergoing plasmapheresis. Results: No major age effects were seen in any of the studied proteins. The Ab 1-42 detectable by xMAP technology appeared to be slightly lower in older donors (Table 1). The results obtained according to donation frequency are presented in table 2. The albumin and IgG content slightly decreased with repeated donations, with no alteration on the donors’ health status. The results of A b content, detectable by xMAP technology, showed no differences or marginal differences (data widely overlapped) when comparing both groups. Conclusions: A slight decrease of albumin and IgG content in repeated donors, as previously known, is confirmed. No major effects on Ab content in correlation to donation frequency could be observed.
Games-Howell post-hoc tests were computed to test for differences between 4 groups of subjects: subjects with consistent CSF and conversion data (both showing pathological, or non-pathological findings), and subjects with discrepant findings (pathological CSF findings but no conversion at follow-up, or vice versa). Results: Of the 389 subjects with complete data sets as to CSF biomarkers and conversion to AD, 121 (31.1%) had discrepant findings between these two outcome measures: While only 7.1% of the subjects with non-pathological CSF findings converted to AD within the 3-year follow-up time, 75.2% did not convert to AD, although they had the AD-typical CSF pathology. Analyses showed that the 4 subject groups were characterised as follows: Subjects with pathological CSF markers who didn’t convert in the 3-year follow-up time were significantly more impaired in the episodic memory tests (word list delayed recall and recognition, p¼<.0001, and .002, respectively), and in the ideational praxis (p¼.013), compared to non-converters with normal CSF findings. MCI subjects with pathological CSF findings and short-term conversion to AD were characterised by a particularly impaired language performance, compared to non-converters with positive or negative CSF findings (p¼.022, and .033, respectively). Conclusions: To predict short-term conversion to AD in subjects with MCI, a characteristic cognitive profile can help improve the predictive validity of CSF findings.
18-28 ( 6 SD) 50-69 ( 6 SD) p value ns: not significant. Table 2 Donation Frequency Effect Donation frequency
P4-347
Albumin (mg/ml)
IgG (mg/ml)
WHICH MCI SUBTYPES CONVERT TO ALZHEIMER’S DISEASE IN SPITE OF NEGATIVE CSF FINDINGS?
Marinella Damian1, Wolfgang Maier2, Christian Luckhaus3, Johannes Kornhuber4, Johannes Pantel5, Michael H€ull6, Holger Jahn7, Johannes Schr€ oder8, Hermann-Josef Gertz9, Harald Hampel10, Alexander Kurz11, Michael Wagner12, Lucrezia Hausner1, Oliver Peters13, Lutz Froelich14, 1Central Institute of Mental Health, Mannheim, Germany; 2 University of Bonn, Bonn, Germany; 3University D€usseldorf, D€usseldorf, Germany; 4University of Erlangen-N€urnberg, Erlangen, Germany; 5 Institute of General Practice, Goethe University Frankfurt, Frankfurt, Germany; 6University of Freiburg ZGGF, Freiburg, Germany; 7University of Hamburg Medical Center, Hamburg, Germany; 8Psychiatrische Universit€ atsklinik Heidelberg, Heidelberg, Germany; 9Klinik und Poliklinik f€ ur Psychiatrie der Universit€at Leipzig, Leipzig, Germany; 10University of Frankfurt, Frankfurt/Main, Germany; 11Technische Universit€at M€unchen, M€ unchen, Germany; 12German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany; 13Charite-Universit€atsmedizin Berlin, Berlin, Germany; 14CIMH Mannheim, Mannheim, Germany. Contact e-mail: [email protected] Background: AD-typical CSF biomarker profiles are often used to predict conversion to AD from mild cognitive impairment (MCI). However, in some MCI subjects, a pathological CSF profile is not as predictive as in others. The aim of this study was to identify the neuropsychological characteristics predicting short-term conversion to AD in spite of negative CSF findings, and no short-term conversion in spite of an AD-typical pathology. Methods: N¼625 subjects were recruited from 13 memory clinics involved in the German Competence Study and followed for up to 3 years. Outcome measures included cognitive variables (e.g. ADAS-cog subtests), conversion to AD, and biological markers (e.g. CSF biomarkers). ANOVAs followed by
P4-348
NEPRILYSIN ACTIVITY IN CSF IS ASSOCIATED WITH CSF TAU BUT NEITHER WITH CEREBRAL AMYLOID LOAD NOR CSF AMYLOID 1-42 IN ALZHEIMER’S DISEASE
Timo Grimmer1, Oliver Goldhardt1, Stefan F€orster2, Alexander Drzezga3, Hans F€orstl4, Alexander Kurz5, Scott Miners6, 1Technische Universit€at M€unchen, Munich, Germany; 2TU Munich, Munich, Germany; 3University of Cologne, Cologne, Germany; 4Technische Universitaet Muenchen, Munich, Germany; 5Technische Universit€at M€unchen, M€unchen, Germany; 6 University of Bristol, Bristol, United Kingdom. Contact e-mail: t. [email protected] Background: Impaired amyloid clearance is a proposed cause of amyloid deposition in sporadic late-onset Alzheimer’s disease (AD). The enzyme Neprilysin is proposed to be primarily responsible for degrading beta-amyloid (A b) in the brain. We aimed to elucidate the role of Neprilysin on invivo brain amyloid load of AD patients using amyloid PET with [11C]PiB and on beta-amyloid1-42 (Ab42) in cerebrospinal fluid (CSF). Methods: Associations between the activity of Neprilysin in CSF, global and regional amyloid load, and concentrations of CSF A b42 and CSF Tau were calculated using linear regression analyses and voxel based analyses with statistical parametric mapping (SPM8), respectively, in 24 AD patients. Results: Neprilysin activity in CSF was not significantly associated with global or regional brain amyloid or CSF A b42 but with CSF Tau (r¼ 0.57, p¼0.004). Conclusions: Impaired amyloid degradation in the brain does not appear to be a major cause of amyloid deposition in sporadic late-onset AD. NEP activity in CSF may be suitable as a marker of neurodegeneration.