Neurology
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Published online before print April 30, 2008, doi:10.1212/01.wnl.0000312383.39973.88)
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Received September 21, 2007
Accepted February 15, 2008

An aberrant protein complex in CSF as a biomarker of Alzheimer disease

M. A. Lovell PhD*, B. C. Lynn PhD, S. Xiong MS, J. F. Quinn MD, J. Kaye MD, and W. R. Markesbery MD

From the Departments of Chemistry (M.A.L., B.C.L.), Pathology (W.R.M.), Neurology (W.R.M.), Sanders-Brown Center on Aging and Alzheimer's Disease Center (M.A.L., S.X., W.R.M.), University of Kentucky, Lexington; and Alzheimer's Disease Center and Department of Neurology (J.F.Q., J.K.), Oregon Health Sciences Center, Portland.


* To whom correspondence should be addressed. E-mail: malove2{at}uky.edu.

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.

Conclusion: 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.






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