An aberrant protein complex in CSF as a biomarker of Alzheimer disease.
OBJECTIVE
To determine if an aberrant protein complex consisting of prostaglandin-d-synthase (PDS) and transthyretin (TTR) in CSF differentiates between subjects with Alzheimer disease (AD) and normal control (NC) subjects.


METHODS
Western blot analysis and a unique sandwich ELISA were used to quantify levels of complexed PDS/TTR in ventricular CSF of subjects with autopsy-verified diagnoses and in lumbar CSF of living subjects with mild to moderate probable AD and age-matched NC subjects. Ventricular CSF was obtained from short postmortem interval autopsies of 7 NC subjects (4 men/3 women), 12 diseased control (DC) subjects (7 men/5 women), 4 subjects with mild cognitive impairment (MCI) (2 men/2 women), and 8 subjects with late-stage AD (LAD) (4 men/4 women). Lumbar CSF was obtained from 15 subjects with probable AD (5 men/10 women) and 14 age-matched NC subjects (10 men/4 women) and was analyzed in a double-blind fashion.


RESULTS
A significant increase in complexed PDS/TTR in ventricular CSF was found in MCI and LAD subjects but not DC subjects compared with NC subjects. Double-blind analysis of complexed PDS/TTR in lumbar CSF showed a significant sixfold increase in levels of the PDS/TTR complex in living probable AD subjects compared with age-matched NC subjects and a 100% sensitivity and 93% specificity in the identification of subjects with AD.


CONCLUSIONS
After further study of larger numbers of patients, quantifying prostaglandin-d-synthase/transthyretin complex in CSF may be useful in the diagnosis of Alzheimer disease, possibly in the early stages of the disease.
Lovell
M A
MA
Department of Chemistry, Sanders-Brown Center on Aging and Alzheimer's Disease Center, University of Kentucky, Lexington, KY 40536-0230, USA. malove2@uky.edu
Lynn
B C
BC
Xiong
S
S
Quinn
J F
JF
Kaye
J
J
Markesbery
W R
WR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002552:Cerebral Ventricles; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000134:cerebrospinal fluid*; D054834:Lipocalins / Q000134:cerebrospinal fluid*; D008297:Male; D046912:Multiprotein Complexes / Q000134:cerebrospinal fluid; D011228:Prealbumin / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D054834:Lipocalins; D046912:Multiprotein Complexes; D011228:Prealbumin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase