Altered glycosylation of acetylcholinesterase in lumbar cerebrospinal fluid of patients with Alzheimer's disease

Abstract We describe an optimized, sensitive assay procedure for simultaneously determining 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, and serotonin in human lumbar cerebrospinal fluid. The assay is based on liquid chromatography with an electrochemical detection system equipped with a newly developed, highly sensitive graphite electrode. Before assay, samples are deproteinized with perchloric acid, 0.2 mol/L. The within- and between-day CVs were less than 2.5% and 6.7%, respectively, for all compounds. The lower limits of detection for 3-methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid were 0.5 pg and for the other three analytes 1.5 pg per injection. Preliminary data on monoaminergic metabolites by the current assay showed that concentrations of dopaminergic and serotonergic metabolites were significantly (P less than 0.05) lower in patients with Alzheimer's disease than in the age-matched controls. In addition, the concentration of 3,4-dihydroxyphenylacetic acid correlated significantly (P less than 0.01) with that of homovanillic acid, suggesting that monitoring either of these metabolites in cerebrospinal fluid can be used as an index of central dopaminergic activity.

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Activities and Kinetic Properties of Lumbar Cerebrospinal Fluid Cholinesterases in Relation to Clinical Diagnosis, Severity, and Progression of Alzheimer's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100029474 ◽

1989 ◽

Vol 16 (4) ◽

pp. 406-410 ◽

Cited By ~ 5

Author(s):

F. Jacob Huff ◽

Clara T. Reiter ◽

Jack Protetch

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Clinical Diagnosis ◽

Ache Activity ◽

Kinetic Properties ◽

Bche Activity ◽

Lumbar Cerebrospinal Fluid ◽

Severity Of Dementia ◽

Over Time

ABSTRACT:Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities of lumbar cerebrospinal fluid (CSF) have been measured in seventeen patients with a clinical diagnosis of probable Alzheimer's disease (Prob AD), possible Alzheimer's disease (Poss AD), or dementia of non-Alzheimer aetiology (Non-AD). The three diagnostic groups did not differ with regard to the Km or saturation kinetic properties of AChE and BChE. The CSF AChE activity was significantly higher in Prob AD than in Non-AD patients. The groups did not differ significantly in BChE activity. The ratio of AChE to BChE activity was significantly higher in both the Prob AD and Poss AD groups than in the Non-AD group, and the ranges of values in the Prob AD and Non-AD groups did not overlap. Among patients in the Prob AD group, severity of dementia was correlated with both AChE activity and the AChE/BChE ratio, and progression of dementia over time was also correlated with AChE/BChE.The AChE/BChE ratio correlated more strongly than AChE with severity and progression of dementia in Prob AD patients, and also better distinguished them from Non-AD patients, suggesting that AChE/BChE may be the more useful marker for diagnosis of AD. It is not clear from the results whether AChE/BChE is useful for diagnosis of the complex dementia cases in the Poss AD group.

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