Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls

Abstract

Several neurotransmitter markers were investigated in the cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) (n = 27), Parkinson's disease (PD) (n = 35) and ALS (n = 26) and from control subjects (n = 34) to compare the possible alterations in the biochemical profiles of these different neurodegenerative diseases. The main proportion of the patients represented an early phase of the illness at the time of the diagnosis. Correlations of the degree of dementia and the stage of the disease with CSF measures were evaluated. The CSF levels of somatostatin like-immunoreactivity (SLI) were significantly reduced in AD patients when compared with those of normals and ALS patients. The CSF concentrations of homovanillic acid (HVA) were significantly decreased for PD patients and the decrease focused on the non-demented patients. A trend of decreasing HVA values towards the most advanced stage of Parkinson's disease assessed by Webster's scale was also displayed. The content of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF was higher for ALS patients than for other groups. The lowest 5-hydroxy-indoleacetic acid (5HIAA) levels were observed in the PD group and the lowest acetylcholinesterase (AChE) activities were found in the PD patients with the most severe disease. Changes in CSF measures were too subtle to be beneficial for diagnostic purposes, but adequate for reflecting the different neurochemical profiles of these three degenerative neurological disorders.

Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson's disease

“…Table 1 presents the 5-S-CyS-DA and HVA levels and the 5-S-CyS-DA/ HVA concentration ratios measured in the CSF of 20 PD patients maintained on Madopar (PD-LT patients), the same patients 5 days after this drug was discontinued (PD-LW patients), and for 16 controls. The mean level of HVA was significantly lower (p = 0.001) in the CSF of PD-LW patients (22.32 _+ 5.08ngmL-~; mean _+ SEM) than in that of controls (46.30 +_ 4.09ngmL I) in agreement with the results of previous studies (Hartikainen et al, 1992;Chia et al, 1993;Gonzalez-Quevedo et al, 1993). After Madopar administration (i.e., PD-LT patients), mean CSF levels of HVA increased to 43.53 _+ 6.20ngmL -1 (p < 0.05 compared to PD-LW patients) and reached approximately the same concentration measured in controls (46.30 _+ 4.09ngmL-1).…”

“…As noted by previous investigators (Hartikainen et al, 1992;Chia et al, 1993;Gonzalez-Quevedo et al, 1993), the mean HVA levels in the CSF of PD-LW patients (22.32 +_ 5.08ngmL -1) was significantly (p = 0.001) lower than that measured in the CSF of controls (46.30 _+ 4.09ngmL-1). The fact that, on average, CSF levels of HVA are reduced by only ca.…”

Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease ? effect of L-Dopa

“…A heterogenous degeneration of multiple neuronal networks may reflect a generalized brain disorder relating to senile dementia of Alzheimer type (SDAT) (Quinn et al, 1986;Jellinger, 1991;Griffiths et al, 1994). Neurochemical and immunohistochemical studies suggest al least three dementia syndromes in PD: the most common is a consequence of dopamine deficiency, another results from combined dopaminergic and cholinergic deficiencies (Kawakatsu et al, 1990;Jellinger, 1986;Konings et al, 1995) and a third represents combined PD and SDAT with an additional varying involvement of other neurotransmitters, like serotonin (Gottfries et al, 1983;Herregodts et al, 1989) and SDAT-typical neuromodulators such as somatostatin (Leake and Ferrier, 1993;Unsicker, 1993;Hartikainen et al, 1992).…”

Somatostatin and Cognitive Function in Neurodegenerative Disorders

“…As regards SLI in the CSF, no change was found between ALS patients and normal subjects [168]. Nieto-Gonzalez et al found a decreased density of parvalbumin-and SST-positive inhibitory interneurones and reduced vesicular GABA transporter immunoreactivity in the neuropil of the wobbler mouse, an animal model of ALS.…”