Alzheimer Disease: van Kamp GJ

Mulder C, Scheltens P, Visser JJ, van Kamp GJ, Schutgens RB. · Department of Clinical Chemistry, University Hospital Vrije Universiteit, Amsterdam, The Netherlands. · Ann Clin Biochem. · Pubmed #11026514 No free full text.

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Mulder C, Schoonenboom NS, Jansen EE, Verhoeven NM, van Kamp GJ, Jakobs C, Scheltens P. · Department of Clinical Chemistry, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. · Neurosci Lett. · Pubmed #16040194 No free full text.

Abstract: Homocysteine accumulation, frequently observed in plasma of AD patients, may be a sign of a reduced activity of the brain methionine-homocysteine transmethylation cycle. S-Adenosylmethionine (SAM) is the main methyl donor in several transmethylation reactions. The demethylated product of SAM, S-adenosylhomocysteine (SAH), is hydrolyzed to yield homocysteine, which can be remethylated to methionine by transfer of a methyl group of 5-methyltetrahydrofolate (5-MTHF). A reduced activity of the transmethylation cycle in the brain may result in hypomethylation of the promoter of the presenilin 1 (PS1) gene, which will lead to overexpression of presenilin 1 and, consequently, to increased Abeta(1-42) (Abeta42) formation. Brain transmethylation was studied in 30 patients with 'probable' AD and 28 age-matched non-demented controls by measuring the cerebrospinal fluid (CSF) levels of SAM, SAH and 5-MTHF. 5-MTHF was determined by HPLC with electrochemical detection, while SAM and SAH were assayed by stable isotope dilution tandem mass spectrometry. We found no statistical differences between AD patients and controls for 5-MTHF, SAM and SAH levels, and the SAM/SAH-ratio in CSF. These findings argue against a possible change in methylation of the promoter and expression of PS1.

Mulder C, Wahlund LO, Teerlink T, Blomberg M, Veerhuis R, van Kamp GJ, Scheltens P, Scheffer PG. · Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. · J Neural Transm. · Pubmed #12898349 No free full text.

Abstract: Choline containing phospholipids are essential for the integrity of the'cell'membrane. Minor changes in the lysophosphatidylcholine (lyso-PC)/phosphatidylcholine (PC) ratio may lead to neuronal damage and cell loss. Several studies have shown protein and lipid oxidation in Alzheimer's disease (AD) affected brain regions. Amyloid-beta peptides may induce free-radical oxidative stress which normally is counteracted by anti-oxidant defense mechanisms. We hypothesize that oxidation may lead to changed concentrations of choline containing phospholipids in cerebrospinal fluid (CSF) of AD patients, because of the susceptibility of the unsaturated acyl-chains of PC for oxidation. PC and lyso-PC were determined in CSF of AD patients (n=19) and subjects with subjective memory complaints without dementia (n=19) by tandem mass spectrometry. No differences in total PC concentrations were observed between both study groups. Furthermore, we could not demonstrate different concentrations of PC species containing linoleic acid and PC species containing arachidonic acid. Interestingly, lyso-PC concentrations tended to be lower while the lyso-PC/PC ratio was significantly decreased in CSF of AD patients compared to controls (0.36% versus 0.54%; P=0.017). A comparable decrease was found for the lyso-PC/PC ratio for PC containing linoleic acid (P=0.022) or arachidonic acid (P=0.010), respectively. The lower lyso-PC/PC ratio in CSF of patients with AD may reflect alterations in the metabolism of choline-containing phospholipids in the brain in AD, and suggests that PC species containing linoleic acid or arachidonic acid are equally involved.

Mulder C, Schoonenboom SN, Wahlund LO, Scheltens P, van Kamp GJ, Veerhuis R, Hack CE, Blomberg M, Schutgens RB, Eikelenboom P. · Department of Clinical Chemistry, Research Institute Neurosciences, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. · J Neural Transm. · Pubmed #12486489 No free full text.

Abstract: Serum amyloid P component (SAP) and complement C1q are found highly co-localized with extracellular fibrillar amyloidbeta (Abeta) deposits in Alzheimer's disease (AD) brain. Conflicting data were reported earlier about the cerebrospinal fluid (CSF) levels of SAP and C1q in AD compared to controls. The objective of the present study was to compare the levels of Abeta(1-42), tau, C1q and SAP in CSF of a well characterized group of AD patients and controls, and to assess the association with dementia severity.Significantly decreased CSF levels of Abeta(1-42) were observed in the AD group (480 +/- 104 ng/L) as compared to controls (1,040 +/- 213 ng/L), whereas tau levels were significantly higher in patients with AD (618 +/- 292 ng/L) than in controls (277 +/- 136 ng/L). Combining the results of Abeta(1-42) and tau measurements resulted in a clear separation between the AD group and the controls. No significant differences in CSF levels of SAP and C1q were observed between the well characterized AD patients and non demented control group. Furthermore, we could not demonstrate a correlation between SAP and C1q CSF levels and the severity of the disease, expressed in Mini-Mental State Examination (MMSE) scores. Therefore, in our opinion these factors can be excluded from the list of potentially interesting biomarkers for AD diagnosis and progression.

Mulder C, Wahlund LO, Blomberg M, de Jong S, van Kamp GJ, Scheltens P, Teerlink T. · Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands, Sweden. · J Neural Transm. · Pubmed #12203047 No free full text.

Abstract: Nitric oxide (NO) may play a role in the pathophysiology of Alzheimer's disease (AD). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is involved in regulation of NO production. Recently it has been reported that dimethylarginine dimethylaminohydrolase, an enzyme that hydrolyses ADMA into citrulline and dimethylamine, is specifically elevated in neurons displaying cytoskeletal abnormalities and oxidative stress in AD. We hypothesized that this could lead to altered CSF concentrations of ADMA in AD. Measurement of ADMA and dimethylamine in CSF revealed no significant differences between AD patients (n = 20) and age-matched control subjects (n = 20). Our results suggest that in early stages of AD overall regulation of NO production by ADMA is not aberrant.