Analysis of cerebrospinal fluid of Alzheimer patients. Biomarkers and toxic properties.
Alzheimer's disease (AD) is a severe, progressive and chronic disorder with strong cognitive deficits. Diagnosis of probable AD can be performed by measuring biomarkers in cerebrospinal fluid (CSF). The aim of the present study was to measure CSF levels of nerve growth factor (NGF), the anti-NGF auto-antibody, and the cholinesterases AChE and BChE, and to correlate them with beta-amyloid, tau and phospho-tau-181. We could show that NGF-like immunoreactivity, but not anti-NGF auto-antibody, was significantly enhanced in AD patients compared to healthy subjects, while both cholinesterases were not changed. beta-Amyloid(1-42) was decreased, while tau and phospho-tau-181 were increased. The commercial Promega NGF ELISA detected mature NGF but not wild-type-human-pro-NGF. Using a bioassay of brain slices, we showed that recombinant mature NGF enhanced survival of cholinergic neurons, while wild-type human pro-NGF displayed a less pronounced effect. The addition of CSF to brain slices exhibited strong toxic effects on the survival of cholinergic neurons. We conclude that in CSF of AD patients (at least partly) mature NGF-like immunoreactivity is enhanced, and is masked in a bioassay by the toxic properties of CSF.
Marksteiner
Josef
J
Department of General Psychiatry, Innsbruck Medical University, Innsbruck, Austria.
Pirchl
Michael
M
Ullrich
Celine
C
Oberbauer
Harald
H
Blasko
Imrich
I
Lederer
Wolfgang
W
Hinterhuber
Hartmann
H
Humpel
Christian
C
D000110:Acetylcholinesterase / Q000134:cerebrospinal fluid; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D001681:Biological Assay / Q000379:methods; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000503:physiopathology*; D002091:Butyrylcholinesterase / Q000134:cerebrospinal fluid; D002470:Cell Survival / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D020932:Nerve Growth Factor / Q000134:cerebrospinal fluid*; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D020932:Nerve Growth Factor; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase