Neurochemical Alterations in Parkinson’s Disease

Chase, Thomas N.

doi:10.1007/978-1-4684-1039-6_16

Cited by 23 publications

(5 citation statements)

References 105 publications

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“…Turnover of dopamine in caudate and putamen makes a major contribution to HVA measured in CSF (Ballenger et al, 1980). Although there are several reports that a reduced CSF HVA concentration is correlated to disease severity and can distinguish PD subjects from healthy controls (Chase, 1980; LeWitt and Galloway, 1990), our measurements of CSF HVA concentration did not confirm these observations.…”

Section: Discussioncontrasting

confidence: 95%

CSF xanthine, homovanillic acid, and their ratio as biomarkers of Parkinson's disease

et al. 2011

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Diminished nigrostriatal dopaminergic neurotransmission is a biochemical hallmark of Parkinson’s disease. Despite this, a reliable trait biomarker of sporadic Parkinson’s disease has not emerged from measurements of cerebrospinal fluid dopamine metabolites. Previous studies have highlighted strong neurochemical relationships between dopamine and various purine compounds. In this study, we analyzed cerebrospinal fluid concentrations of homovanillic acid (the major catabolite of dopamine) and the purine compound xanthine for a comparison of 217 unmedicated Parkinson’s disease subjects and 26 healthy controls. These compounds were highly correlated for both the Parkinson’s disease subjects (r=0.68) and for controls (r=0.73; both groups, p<0.001). While neither homovanillic acid nor xanthine concentrations differentiated Parkinson’s disease from controls, their ratio did. For controls, the mean [xanthine]/[homovanillic acid] quotient was 13.1±5.5 as compared to the Parkinson’s disease value of 17.4±6.7 at an initial lumbar CSF collection (p=0.0017), and 19.7±8.7 (p<0.001) at a second CSF collection up to 24 months later. The [xanthine]/[homovanillic acid] ratio in the Parkinson’s disease subjects differed as a function of disease severity, as measured by the sum of Unified Parkinson’s Disease Rating Scale Activities of Daily Living and Motor Exam ratings. The [xanthine]/[homovanillic acid] ratio also increased between the first and second CSF collections, suggesting that this quotient provides both a state and trait biomarker of Parkinson’s disease. These observations add to other neurochemical evidence that links purine metabolism to Parkinson’s disease.

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Section: Discussioncontrasting

confidence: 95%

CSF xanthine, homovanillic acid, and their ratio as biomarkers of Parkinson's disease

et al. 2011

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“…Thus, in our study, mean levels of HVA in CSF were pathognomonic of Parkinson's disease, distinguishing patients from volunteers, while p-MIAA levels reflected the severity of the disease. Previous attempts to relate clinical characteristics, including severity, of Parkinson's disease with levels of HVA in lumbar CSF have yielded inconsistent results (Chase, 1980), probably because the variables controlling HVA levels in lumbar CSF obfuscate the contribution from brain (see Degrell and Nagy, 1990).…”

Section: Discussionmentioning

confidence: 99%

Levels ofpros-methylimidazoleacetic acid: Correlation with severity of Parkinson's disease in CSF of patients and with the depletion of striatal dopamine and its metabolites in MPTP-treated mice

Prell

Khandelwal

Burns

et al. 1991

J Neural Transm Gen Sect

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The cerebrospinal fluid (CSF) levels of pros-methylimidazoleacetic acid (p-MIAA) in thirteen medication-free patients with mild to moderate Parkinson's disease were highly correlated (Spearman's rho = 0.749, p less than 0.005) with the severity of signs of the disease as scored on the Columbia University Rating Scale. Levels of p-MIAA in males (n = 8) and females (n = 5) were each significantly correlated with scores of severity (rho = 0.78, p less than 0.05 and rho = 1.0, p less than 0.05, respectively). In C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), levels of p-MIAA were significantly correlated with the depleted levels of dopamine (r = 0.85, p less than 0.01), homovanillic acid (r = 0.79, p less than 0.02), 3,4-dihydroxyphenylacetic acid (r = 0.84, p less than 0.01) and norepinephrine (r = 0.91, p less than 0.002) in striatum, but not in cortex of the same mice. No such correlations were observed in either striatum or cortex of saline-treated control mice. Mean levels of p-MIAA in CSF did not differ significantly between patients and age-matched controls; and mean levels of p-MIAA in striatum did not differ between MPTP-treated mice and controls. The simplest hypothesis to account for these strong correlations in the absence of differences in mean levels of p-MIAA is that accumulation of p-MIAA [or process(es) that govern its accumulation] influences a failing nigrostriatal system. It is also possible (in analogy with findings in other diseases and with other drugs) that measurements of the putative metabolite(s) of p-MIAA may distinguish the patients and the MPTP-treated mice from their respective controls. Elucidation of the processes that regulate formation and disposition of p-MIAA in brain and information on the neural effects of p-MIAA, its precursors and its putative metabolites may yield insight into factors that regulate the progression of Parkinson's disease, and may shed additional light on the cause(s) of this disease.

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“…Although the low CSF HVA levels in most affected individuals indicate dysfunction of dopamine pathways in the central nervous system, levels did not always correlate with disease status (see Table 1). Thus, although HVA levels may be abnormal in RDP, as they appear to be in DRD, 3 PD, 31 and juvenile PD, 32 they do not provide a reliable clinical assay for diagnosis or determination of gene carrier status in these two families.…”

Section: Discussionmentioning

confidence: 99%

Rapid-onset dystonia-parkinsonism: Linkage to chromosome 19q13

et al. 1999

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Rapid‐onset dystonia–parkinsonism (RPD) is an autosomal dominant movement disorder characterized by sudden onset of persistent dystonia and parkinsonism, generally during adolescence or early adulthood. Symptoms evolve over hours or days, and generally stabilize within a few weeks, with slow or no progression. Other features include little or no response to L‐dopa, and low levels of homovanillic acid in the central nervous system. Neuroimaging studies indicate no degeneration of dopaminergic nerve terminals in RDP, suggesting that this disorder results from a functional deficit, as in dystonia, rather than neuronal loss, as in Parkinson's disease. We studied 81 members of two midwestern US families with RDP, 16 of whom exhibited classic features of RDP. We found significant evidence for linkage in these two families to markers on chromosome 19q13, with the highest multipoint LOD score at D19S198 (z = 5.77 at θ = 0.0). The flanking markers D19S587 and D19S900 define a candidate region of approximately 8 cM. Although RDP itself is a rare condition, it is important because it has clinical and biochemical similarities to both Parkinson's disease and dystonia. Identification of the genetic defect in RDP holds promise for understanding the underlying disease processes of both of these more common diseases. Ann Neurol 1999;46:176–182

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Neurochemical Alterations in Parkinson’s Disease

Cited by 23 publications

References 105 publications

CSF xanthine, homovanillic acid, and their ratio as biomarkers of Parkinson's disease

CSF xanthine, homovanillic acid, and their ratio as biomarkers of Parkinson's disease

Levels ofpros-methylimidazoleacetic acid: Correlation with severity of Parkinson's disease in CSF of patients and with the depletion of striatal dopamine and its metabolites in MPTP-treated mice

Rapid-onset dystonia-parkinsonism: Linkage to chromosome 19q13

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