Reduced cerebrospinal fluid dynorphin A1-8 in Alzheimer's disease.
Cerebrospinal fluid (CSF) measures of dynorphin A were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p less than 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo.
Sunderland
T
T
Unit of Geriatric Psychopharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Berrettini
W H
WH
Molchan
S E
SE
Lawlor
B A
BA
Martinez
R A
RA
Vitiello
B
B
Tariot
P N
PN
Cohen
R M
RM
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology; D001921:Brain / Q000503:physiopathology; D003866:Depressive Disorder / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000523:psychology; D004399:Dynorphins / Q000134:cerebrospinal fluid*; D005260:Female; D019004:Galanin; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D011939:Mental Recall / Q000502:physiology; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009478:Neuropeptide Y / Q000134:cerebrospinal fluid; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010455:Peptides / Q000134:cerebrospinal fluid; D011957:Receptors, Opioid / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000134:cerebrospinal fluid
D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D011957:Receptors, Opioid; D014660:Vasoactive Intestinal Peptide; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D004399:Dynorphins; C026770:dynorphin (1-8); D019004:Galanin; D006719:Homovanillic Acid