Age-related changes in cerebrospinal fluid protein concentrations

Garton, Mark; Keir, Geoffrey; Lakshmi, M. Vijaya; Thompson, Edward J.

doi:10.1016/0022-510x(91)90218-v

Cited by 93 publications

(52 citation statements)

References 19 publications

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“…In adult animals KYNA does not or very slightly penetrates through the blood-brain barrier (BBB) [49] . With increasing age of the subjects analysed, a moderate increase of BBB permeability was observed in line with previously published data [50] , and a slightly positive relationship between CSF:serum albumin concentrations ratio and ageing or CSF KYNA levels would not exclude a very moderate diffusion of KYNA into the aged CNS. Since no difference in KYNA serum level was found in subjects investigated, we would suggest that CSF KYNA increases with advancing age originate from the brain.…”

Section: Discussionsupporting

confidence: 89%

Age-Related Increase of Kynurenic Acid in Human Cerebrospinal Fluid – IgG and β<sub>2</sub>-Microglobulin Changes

et al. 2005

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Kynurenic acid (KYNA) is an endogenous metabolite in the kynurenine pathway of tryptophan degradation and is an antagonist at the glycine site of the N-methyl-D-aspartate as well as at the alpha 7 nicotinic cholinergic receptors. In the brain tissue KYNA is synthesised from L-kynurenine by kynurenine aminotransferases (KAT) I and II. A host of immune mediators influence tryptophan degradation. In the present study, the levels of KYNA in cerebrospinal fluid (CSF) and serum in a group of human subjects aged between 25 and 74 years were determined by using a high performance liquid chromatography method. In CSF and serum KAT I and II activities were investigated by radioenzymatic assay, and the levels of β₂-microglobulin, a marker for cellular immune activation, were determined by ELISA. The correlations between neurochemical and biological parameters were evaluated. Two subject groups with significantly different ages, i.e. <50 years and >50 years, p < 0.001, showed statistically significantly different CSF KYNA levels, i.e. 2.84 ± 0.16 fmol/µl vs. 4.09 ± 0.14 fmol/µl, p < 0.001, respectively; but this difference was not seen in serum samples. Interestingly, KYNA is synthesised in CSF principally by KAT I and not KAT II, however no relationship was found between enzyme activity and ageing. A positive relationship between CSF KYNA levels and age of subjects indicates a 95% probability of elevated CSF KYNA with ageing (R = 0.6639, p = 0.0001). KYNA levels significantly correlated with IgG and β₂-microglobulin levels (R = 0.5244, p = 0.0049; R = 0.4253, p = 0.043, respectively). No correlation was found between other biological parameters in CSF or serum. In summary, a positive relationship between the CSF KYNA level and ageing was found, and the data would suggest age-dependent increase of kynurenine metabolism in the CNS. An enhancement of CSF IgG and β₂-microglobulin levels would suggest an activation of the immune system during ageing. Increased KYNA metabolism may be involved in the hypofunction of the glutamatergic and/or nicotinic cholinergic neurotransmission in the ageing CNS.

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Section: Discussionsupporting

confidence: 89%

Age-Related Increase of Kynurenic Acid in Human Cerebrospinal Fluid – IgG and β<sub>2</sub>-Microglobulin Changes

et al. 2005

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“…This supports the hypothesis of a sustained function of the blood-brain barrier in AD in amino acid transport, with no specific changes detectable on the brain side [23].…”

Section: Discussionsupporting

confidence: 86%

Alanyl-Aminopeptidase Activity Decrease in Cerebrospinal Fluid of Alzheimer Patients

Iribar¹,

Montes²,

Maldonado³

et al. 1997

Dement Geriatr Cogn Disord

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We analyzed the amino acid concentrations and aminopeptidase activities in plasma and the cerebrospinal fluid (CSF) of Alzheimer patients. Correlations were calculated between these parameters and the degree of cognitive impairment, duration of the disease and age. In comparison with a control group, no changes were found in the levels of amino acids in CSF or plasma of Alzheimer patients. Alanyl-aminopeptidase activity was significantly lower in the CSF of Alzheimer patients, whereas no differences in CSF were detected as regards the remaining aminopeptidases. The plasma/CSF ratio for aminopeptidase activities was higher in AD patients than in controls, although the difference was only significant for alanyl-aminopeptidase. Amino acid ratios did not show this general tendency. The correlations between plasma aspartate and glutamate concentrations and the stage of the disease, measured with the Mini Mental State Examination, were studied. Changes in aminopeptidase activities and their role in protein dysfunction underlying Alzheimer disease are discussed.

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“…SAP is synthesized by hepatocytes and since a local synthesis of SAP has not been detectable in the central nervous system [24,25], the SAP localized in the plaques of AD patients is probably plasma-derived. It is well known that the permeability of the blood-brain barrier increases with age [26], and this combined with an elevated plasma SAP concentration could lead to an increase in SAP levels in the cerebrospinal fluid with increasing age, as recently reported for AD patients [18].…”

Section: Discussionmentioning

confidence: 62%

Increased Plasma Concentration of Serum Amyloid P Component in Centenarians with Impaired Cognitive Performance

Nybo¹,

Olsen²,

Jeune³

et al. 1998

Dement Geriatr Cogn Disord

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Serum amyloid P component (SAP) binds to all amyloid fibrils including those in the plaques and tangles of Alzheimer patients. To investigate whether the plasma SAP concentration correlated to cognitive impairment, we measured SAP levels in blood samples from 41 centenarians and compared these to the cognitive performance evaluated by Mini Mental State Examination (MMSE). We observed a significantly (p < 0.001) increased SAP concentration (48.3 ± 16.9 µg/ml; mean ± SD) in the centenarians compared to gender-matched controls (32.8 ± 11.4 µg/ml). Six severely demented centenarians had an even higher SAP concentration (60.2 µg/ml), while the subgroup of cognitive intact centenarians (MMSE score >24) showed a normal SAP concentration (38.4 ± 9.3 µg/ml). No dehydration or hepatic dysfunction was demonstrable in the centenarians. We conclude that the centenarians with impaired cognitive performance had significantly increased plasma concentrations of SAP, while the values for cognitive intact centenarians were within the normal range.

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Age-related changes in cerebrospinal fluid protein concentrations

Cited by 93 publications

References 19 publications

Age-Related Increase of Kynurenic Acid in Human Cerebrospinal Fluid – IgG and β<sub>2</sub>-Microglobulin Changes

Age-Related Increase of Kynurenic Acid in Human Cerebrospinal Fluid – IgG and β<sub>2</sub>-Microglobulin Changes

Alanyl-Aminopeptidase Activity Decrease in Cerebrospinal Fluid of Alzheimer Patients

Increased Plasma Concentration of Serum Amyloid P Component in Centenarians with Impaired Cognitive Performance

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