Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.
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Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease. / Arlt, Sönke; Schwedhelm, Edzard; Kölsch, Heike; Jahn, Holger; Linnebank, Michael; Smulders, Yvo; Jessen, Frank; Böger, Rainer; Popp, Julius.
in: J ALZHEIMERS DIS, Jahrgang 31, Nr. 4, 4, 2012, S. 751-758.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.
AU - Arlt, Sönke
AU - Schwedhelm, Edzard
AU - Kölsch, Heike
AU - Jahn, Holger
AU - Linnebank, Michael
AU - Smulders, Yvo
AU - Jessen, Frank
AU - Böger, Rainer
AU - Popp, Julius
PY - 2012
Y1 - 2012
N2 - Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-? 1-42 (A?42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF A?42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to A?42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.
AB - Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-? 1-42 (A?42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF A?42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to A?42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Adolescent
KW - Young Adult
KW - Alzheimer Disease/blood/cerebrospinal fluid/diagnosis
KW - Arginine/analogs & derivatives/blood/cerebrospinal fluid
KW - Biological Markers/blood/cerebrospinal fluid
KW - Homocysteine/blood/cerebrospinal fluid
KW - S-Adenosylmethionine/blood/cerebrospinal fluid
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Adolescent
KW - Young Adult
KW - Alzheimer Disease/blood/cerebrospinal fluid/diagnosis
KW - Arginine/analogs & derivatives/blood/cerebrospinal fluid
KW - Biological Markers/blood/cerebrospinal fluid
KW - Homocysteine/blood/cerebrospinal fluid
KW - S-Adenosylmethionine/blood/cerebrospinal fluid
M3 - SCORING: Journal article
VL - 31
SP - 751
EP - 758
JO - J ALZHEIMERS DIS
JF - J ALZHEIMERS DIS
SN - 1387-2877
IS - 4
M1 - 4
ER -
