title: Neuropeptide changes and neuroactive amino acids in CSF from humans and sheep with neuronal ceroid lipofuscinoses (NCLs, Batten disease).
abstract: Anomalies in neuropeptides and neuroactive amino acids have been postulated to play a role in neurodegeneration in a variety of diseases including the inherited neuronal ceroid lipofuscinoses (NCLs, Batten disease). These are often indicated by concentration changes in cerebrospinal fluid (CSF). Here we compare CSF neuropeptide concentrations in patients with the classical juvenile CLN3 form of NCL and the classical late infantile CLN2 form with neuropeptide and neuroactive amino acid concentrations in CSF from sheep with the late infantile variant CLN6 form. A marked disease related increase in CSF concentrations of neuron specific enolase and tau protein was noted in the juvenile CLN3 patients but this was not observed in an advanced CLN2 patient nor CLN6 affected sheep. No changes were noted in S-100b, GFAP or MBP in patients or of S-100b, GFAP or IGF-1 in affected sheep. There were no disease related changes in CSF concentrations of the neuroactive amino acids, aspartate, glutamate, serine, glutamine, glycine, taurine and GABA in these sheep. The changes observed in the CLN3 patients may be progressive markers of neurodegeneration, or of underlying metabolic changes perhaps associated with CLN3 specific changes in neuroactive amino acids, as have been postulated. The lack of changes in the CLN2 and CLN6 subjects indicate that these changes are not shared by the CLN2 or CLN6 forms and changes in CSF concentrations of these compounds are unreliable as biomarkers of neurodegeneration in the NCLs in general.
authors: Agriculture and Life Sciences Faculty, Lincoln University, Lincoln 7647, New Zealand.
authors: Graham W
authors: GW
authors: Kay
authors: Marcel M
authors: MM
authors: Verbeek
authors: Julie M
authors: JM
authors: Furlong
authors: Michèl A A P
authors: MA
authors: Willemsen
authors: David N
authors: DN
authors: Palmer
mesh_terms: D000367:Age Factors; D000596:Amino Acids / Q000032:analysis / Q000134:cerebrospinal fluid*; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000134:cerebrospinal fluid; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000134:cerebrospinal fluid; D008297:Male; D004676:Myelin Basic Protein / Q000032:analysis / Q000134:cerebrospinal fluid; D009414:Nerve Growth Factors / Q000032:analysis / Q000134:cerebrospinal fluid; D009472:Neuronal Ceroid-Lipofuscinoses / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D009479:Neuropeptides / Q000032:analysis / Q000134:cerebrospinal fluid*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000134:cerebrospinal fluid*; D010751:Phosphopyruvate Hydratase / Q000032:analysis / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis / Q000134:cerebrospinal fluid; D012756:Sheep; D000091346:Tripeptidyl-Peptidase 1; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D000091346:Tripeptidyl-Peptidase 1; D016875:tau Proteins; D007334:Insulin-Like Growth Factor I; C000717267:TPP1 protein, human; D010751:Phosphopyruvate Hydratase