Inositol monophosphatase activity in normal, Down syndrome and dementia of the Alzheimer type CSF.
Inositol monophosphatase (IMPase), a cytoplasmic enzyme that hydrolyses inositol monophosphates to produce inositol is also found in the cerebrospinal fluid (CSF). Since levels of inositol have been previously reported to be elevated in Down syndrome (DS) CSF, IMPase activity was measured in CSF of DS subjects to establish whether altered inositol levels may be related to changes in IMPase activity. In addition, and to better understand the regulation of IMPase expression in the CSF, enzyme activity was measured in normal aging, patients with Alzheimer-type or multi-infarct dementia (DAT and MID, respectively) and in CSF obtained by repeat lumbar puncture or from sequential aliquots of CSF from along the rostro-caudal axis. IMPase activity was relatively constant in CSF obtained from repeated lumbar puncture and there was no significant rostro-caudal gradient of activity in either normal or DS subjects, indicating that the enzyme originates from both brain and spinal cord. Compared to respective age-matched normal subjects, CSF IMPase activity was unaltered in DS, DAT and MID. However, in normal volunteers there was a significant positive correlation between age and CSF IMPase activity. Furthermore, there were significant correlations between CSF IMPase activity and acetylcholinesterase and butyrylcholinesterase activities and total protein, suggesting co-regulation of these parameters within the CSF.
Atack
John R
JR
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom. john_atack@merck.com
Schapiro
Mark B
MB
D000110:Acetylcholinesterase / Q000134:cerebrospinal fluid; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000201:enzymology*; D000704:Analysis of Variance; D002091:Butyrylcholinesterase / Q000134:cerebrospinal fluid; D004314:Down Syndrome / Q000134:cerebrospinal fluid* / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D010744:Phosphoric Monoester Hydrolases / Q000134:cerebrospinal fluid*; D011446:Prospective Studies; D012044:Regression Analysis; D013129:Spinal Puncture / Q000706:statistics & numerical data; D013997:Time Factors
D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase