Effects of time and cholinesterase inhibitor treatment on multiple cerebrospinal fluid parameters in Alzheimer's disease
Development of neuropathology in Alzheimer's disease (AD) cannot be studied directly in living patients. Therefore, concentrations in cerebrospinal fluid (CSF) of the proteins tau, A beta 42, alpha 1-ACT, apoE and other molecules have been analyzed to elucidate their possible role in degenerati...
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| Veröffentlicht in: | Methods and Findings in Experimental and Clinical Pharmacology 1999-10, Vol.21 (8), p.549-554 |
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| creator | MORIEARTY, P. L SEUBERT, P GALASKO, D MARKWELL, S UNNI, L VICARI, S BECKER, R. E |
| description | Development of neuropathology in Alzheimer's disease (AD) cannot be studied directly in living patients. Therefore, concentrations in cerebrospinal fluid (CSF) of the proteins tau, A beta 42, alpha 1-ACT, apoE and other molecules have been analyzed to elucidate their possible role in degeneration and as biomarkers of the disease. To date, however, studies have not analyzed multiple markers in the same patients over time and as a function of pharmacological interventions. In the present investigation we measured CSF tau, A beta 42, alpha 1-ACT, apoE, total protein and electrophoretic fractions, and leukocytes, as well as MMSE, in 12 AD patients of known APOE phenotype. Two or three CSF examinations were performed during periods of up to 2 1/2 years, while subjects were on and off treatment with the cholinesterase inhibitor (ChEI) metrifonate (MTF). CSF A beta 42 and tau levels were in agreement with clinical diagnosis of AD in all patients. Abnormally high proportions of monocytes were found in CSF at baseline, and these proportions correlated positively with plasma alpha 1-ACT and MMSE scores. A small but significant increase in CSF alpha 1-ACT, which correlated with peripheral alpha 1-ACT, was associated with 6 months' MTF treatment, though alpha 1-ACT levels did not change further when treatment continued for 2 years. Monocyte proportions in CSF declined over time in both treated and untreated patients. Among 5 of 6 patients treated for 2 years or more with MTF, CSF measures remained relatively stable. One patient had changes in CSF parameters apparently associated with a transient ischemic attack. Our findings did not indicate that slowed cognitive decline with MTF treatment is associated with systematic change in any CSF marker analyzed. The results suggest that further investigations of the relationship of tau, A beta 42 and cellular abnormalities in CSF early in the course of AD are warranted. |
| doi_str_mv | 10.1358/mf.1999.21.8.794837 |
| format | Article |
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L ; SEUBERT, P ; GALASKO, D ; MARKWELL, S ; UNNI, L ; VICARI, S ; BECKER, R. E</creator><creatorcontrib>MORIEARTY, P. L ; SEUBERT, P ; GALASKO, D ; MARKWELL, S ; UNNI, L ; VICARI, S ; BECKER, R. E</creatorcontrib><description>Development of neuropathology in Alzheimer's disease (AD) cannot be studied directly in living patients. Therefore, concentrations in cerebrospinal fluid (CSF) of the proteins tau, A beta 42, alpha 1-ACT, apoE and other molecules have been analyzed to elucidate their possible role in degeneration and as biomarkers of the disease. To date, however, studies have not analyzed multiple markers in the same patients over time and as a function of pharmacological interventions. In the present investigation we measured CSF tau, A beta 42, alpha 1-ACT, apoE, total protein and electrophoretic fractions, and leukocytes, as well as MMSE, in 12 AD patients of known APOE phenotype. Two or three CSF examinations were performed during periods of up to 2 1/2 years, while subjects were on and off treatment with the cholinesterase inhibitor (ChEI) metrifonate (MTF). CSF A beta 42 and tau levels were in agreement with clinical diagnosis of AD in all patients. Abnormally high proportions of monocytes were found in CSF at baseline, and these proportions correlated positively with plasma alpha 1-ACT and MMSE scores. A small but significant increase in CSF alpha 1-ACT, which correlated with peripheral alpha 1-ACT, was associated with 6 months' MTF treatment, though alpha 1-ACT levels did not change further when treatment continued for 2 years. Monocyte proportions in CSF declined over time in both treated and untreated patients. Among 5 of 6 patients treated for 2 years or more with MTF, CSF measures remained relatively stable. One patient had changes in CSF parameters apparently associated with a transient ischemic attack. Our findings did not indicate that slowed cognitive decline with MTF treatment is associated with systematic change in any CSF marker analyzed. The results suggest that further investigations of the relationship of tau, A beta 42 and cellular abnormalities in CSF early in the course of AD are warranted.</description><identifier>ISSN: 0379-0355</identifier><identifier>ISSN: 2013-0155</identifier><identifier>DOI: 10.1358/mf.1999.21.8.794837</identifier><identifier>PMID: 10599054</identifier><language>eng</language><publisher>Barcelona: Prous</publisher><subject>Aged ; alpha 1-Antichymotrypsin - cerebrospinal fluid ; Alzheimer Disease - cerebrospinal fluid ; Alzheimer Disease - drug therapy ; Alzheimer Disease - pathology ; Amyloid beta-Peptides - cerebrospinal fluid ; Apolipoproteins E - cerebrospinal fluid ; Biological and medical sciences ; Biomarkers - blood ; Biomarkers - cerebrospinal fluid ; Cholinesterase Inhibitors - therapeutic use ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Double-Blind Method ; Electrophoresis ; Female ; Humans ; Intelligence Tests ; Leukocytes - physiology ; Male ; Medical sciences ; Monocytes - physiology ; Neurology ; Phenotype ; tau Proteins - blood ; tau Proteins - cerebrospinal fluid ; Time Factors ; Trichlorfon - therapeutic use</subject><ispartof>Methods and Findings in Experimental and Clinical Pharmacology, 1999-10, Vol.21 (8), p.549-554</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c330t-312ab746061cc8d0d0c5c3154c0891fb112fde433490bd2bc0f1a6c7280e128e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,776,780,785,786,23909,23910,25118,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1178366$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10599054$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MORIEARTY, P. L</creatorcontrib><creatorcontrib>SEUBERT, P</creatorcontrib><creatorcontrib>GALASKO, D</creatorcontrib><creatorcontrib>MARKWELL, S</creatorcontrib><creatorcontrib>UNNI, L</creatorcontrib><creatorcontrib>VICARI, S</creatorcontrib><creatorcontrib>BECKER, R. E</creatorcontrib><title>Effects of time and cholinesterase inhibitor treatment on multiple cerebrospinal fluid parameters in Alzheimer's disease</title><title>Methods and Findings in Experimental and Clinical Pharmacology</title><addtitle>Methods Find Exp Clin Pharmacol</addtitle><description>Development of neuropathology in Alzheimer's disease (AD) cannot be studied directly in living patients. Therefore, concentrations in cerebrospinal fluid (CSF) of the proteins tau, A beta 42, alpha 1-ACT, apoE and other molecules have been analyzed to elucidate their possible role in degeneration and as biomarkers of the disease. To date, however, studies have not analyzed multiple markers in the same patients over time and as a function of pharmacological interventions. In the present investigation we measured CSF tau, A beta 42, alpha 1-ACT, apoE, total protein and electrophoretic fractions, and leukocytes, as well as MMSE, in 12 AD patients of known APOE phenotype. Two or three CSF examinations were performed during periods of up to 2 1/2 years, while subjects were on and off treatment with the cholinesterase inhibitor (ChEI) metrifonate (MTF). CSF A beta 42 and tau levels were in agreement with clinical diagnosis of AD in all patients. Abnormally high proportions of monocytes were found in CSF at baseline, and these proportions correlated positively with plasma alpha 1-ACT and MMSE scores. A small but significant increase in CSF alpha 1-ACT, which correlated with peripheral alpha 1-ACT, was associated with 6 months' MTF treatment, though alpha 1-ACT levels did not change further when treatment continued for 2 years. Monocyte proportions in CSF declined over time in both treated and untreated patients. Among 5 of 6 patients treated for 2 years or more with MTF, CSF measures remained relatively stable. One patient had changes in CSF parameters apparently associated with a transient ischemic attack. Our findings did not indicate that slowed cognitive decline with MTF treatment is associated with systematic change in any CSF marker analyzed. The results suggest that further investigations of the relationship of tau, A beta 42 and cellular abnormalities in CSF early in the course of AD are warranted.</description><subject>Aged</subject><subject>alpha 1-Antichymotrypsin - cerebrospinal fluid</subject><subject>Alzheimer Disease - cerebrospinal fluid</subject><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - pathology</subject><subject>Amyloid beta-Peptides - cerebrospinal fluid</subject><subject>Apolipoproteins E - cerebrospinal fluid</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>Cholinesterase Inhibitors - therapeutic use</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Double-Blind Method</subject><subject>Electrophoresis</subject><subject>Female</subject><subject>Humans</subject><subject>Intelligence Tests</subject><subject>Leukocytes - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Monocytes - physiology</subject><subject>Neurology</subject><subject>Phenotype</subject><subject>tau Proteins - blood</subject><subject>tau Proteins - cerebrospinal fluid</subject><subject>Time Factors</subject><subject>Trichlorfon - therapeutic use</subject><issn>0379-0355</issn><issn>2013-0155</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE9rFTEUR7NQ2lr7CQqShejqjbnJZCZZllL_QMGNXYdM5oYXSWbGJAPqp2_Ke6Cruzm_A_cQcgusAyHVp-Q70Fp3HDrVjbpXYnxFrpgY9YEJKS_Jm1J-MsZBCnlBLoFJrZnsr8jvB-_R1UJXT2tISO0yU3dcY1iwVMy2IA3LMUyhrpnWjLYmXCpdF5r2WMMWkTrMOOW1bGGxkfq4h5luNtuETVDanN7Fv0ds9vyx0DkUbNa35LW3seDN-V6Tp88PP-6_Hh6_f_l2f_d4cEKwehDA7TT2AxvAOTWzmTnpBMjeMaXBTwDcz9gL0Ws2zXxyzIMd3MgVQ-AKxTX5cPJuef21t59MCsVhjHbBdS9m0GLo-cAaKE6ga6-UjN5sOSSb_xhg5iWySd68RDYcjDKnyG317qzfp4Tzf5tT4Qa8PwO2OBt9tosL5R8HoxLDIJ4BqQaJfg</recordid><startdate>19991001</startdate><enddate>19991001</enddate><creator>MORIEARTY, P. 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E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-312ab746061cc8d0d0c5c3154c0891fb112fde433490bd2bc0f1a6c7280e128e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Aged</topic><topic>alpha 1-Antichymotrypsin - cerebrospinal fluid</topic><topic>Alzheimer Disease - cerebrospinal fluid</topic><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - pathology</topic><topic>Amyloid beta-Peptides - cerebrospinal fluid</topic><topic>Apolipoproteins E - cerebrospinal fluid</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - cerebrospinal fluid</topic><topic>Cholinesterase Inhibitors - therapeutic use</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Double-Blind Method</topic><topic>Electrophoresis</topic><topic>Female</topic><topic>Humans</topic><topic>Intelligence Tests</topic><topic>Leukocytes - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Monocytes - physiology</topic><topic>Neurology</topic><topic>Phenotype</topic><topic>tau Proteins - blood</topic><topic>tau Proteins - cerebrospinal fluid</topic><topic>Time Factors</topic><topic>Trichlorfon - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MORIEARTY, P. L</creatorcontrib><creatorcontrib>SEUBERT, P</creatorcontrib><creatorcontrib>GALASKO, D</creatorcontrib><creatorcontrib>MARKWELL, S</creatorcontrib><creatorcontrib>UNNI, L</creatorcontrib><creatorcontrib>VICARI, S</creatorcontrib><creatorcontrib>BECKER, R. 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To date, however, studies have not analyzed multiple markers in the same patients over time and as a function of pharmacological interventions. In the present investigation we measured CSF tau, A beta 42, alpha 1-ACT, apoE, total protein and electrophoretic fractions, and leukocytes, as well as MMSE, in 12 AD patients of known APOE phenotype. Two or three CSF examinations were performed during periods of up to 2 1/2 years, while subjects were on and off treatment with the cholinesterase inhibitor (ChEI) metrifonate (MTF). CSF A beta 42 and tau levels were in agreement with clinical diagnosis of AD in all patients. Abnormally high proportions of monocytes were found in CSF at baseline, and these proportions correlated positively with plasma alpha 1-ACT and MMSE scores. A small but significant increase in CSF alpha 1-ACT, which correlated with peripheral alpha 1-ACT, was associated with 6 months' MTF treatment, though alpha 1-ACT levels did not change further when treatment continued for 2 years. Monocyte proportions in CSF declined over time in both treated and untreated patients. Among 5 of 6 patients treated for 2 years or more with MTF, CSF measures remained relatively stable. One patient had changes in CSF parameters apparently associated with a transient ischemic attack. Our findings did not indicate that slowed cognitive decline with MTF treatment is associated with systematic change in any CSF marker analyzed. The results suggest that further investigations of the relationship of tau, A beta 42 and cellular abnormalities in CSF early in the course of AD are warranted.</abstract><cop>Barcelona</cop><pub>Prous</pub><pmid>10599054</pmid><doi>10.1358/mf.1999.21.8.794837</doi><tpages>6</tpages></addata></record> |
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| ispartof | Methods and Findings in Experimental and Clinical Pharmacology, 1999-10, Vol.21 (8), p.549-554 |
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| subjects | Aged alpha 1-Antichymotrypsin - cerebrospinal fluid Alzheimer Disease - cerebrospinal fluid Alzheimer Disease - drug therapy Alzheimer Disease - pathology Amyloid beta-Peptides - cerebrospinal fluid Apolipoproteins E - cerebrospinal fluid Biological and medical sciences Biomarkers - blood Biomarkers - cerebrospinal fluid Cholinesterase Inhibitors - therapeutic use Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Double-Blind Method Electrophoresis Female Humans Intelligence Tests Leukocytes - physiology Male Medical sciences Monocytes - physiology Neurology Phenotype tau Proteins - blood tau Proteins - cerebrospinal fluid Time Factors Trichlorfon - therapeutic use |
| title | Effects of time and cholinesterase inhibitor treatment on multiple cerebrospinal fluid parameters in Alzheimer's disease |
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