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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.
Address correspondence and reprint requests to Dr. Mark A. Lovell, 135 Sanders-Brown Building, 800 S. Limestone St., Lexington, KY 40536-0230 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.
Abbreviations: 2D = two-dimensional; AD = Alzheimer disease; ADRDA = Alzheimer Disease and Related Disorders Association; APP = amyloid precursor protein; AUC = area under the curve; CERAD = Consortium to Establish a Registry for Alzheimer’s Disease; DC = diseased control; DLB = dementia with Lewy bodies; FAP = familial amyloid polyneuropathy; FTD = frontotemporal dementia; GAP-43 = growth associated protein 43; LAD = late-stage AD; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; MW = molecular weight; NC = normal control; NF = neurofilament; NIA-RI = National Institute on Aging-Reagan Institute; NINCDS = National Institute of Neurological and Communicative Disorders and Stroke; NTP = neural thread protein; PD = Parkinson disease; PDS = prostaglandin-d-synthase; PSP = progressive supranuclear palsy; ROC = receiver operating characteristic; TTR = transthyretin; UK-ADC = University of Kentucky Alzheimer’s Disease Center.
Supplemental data at www.neurology.org
e-Pub ahead of print on April 30, 2008, at www.neurology.org.
Supported by NIH grants 5P30-AG 028383 and 5P50-AG 05144, NIA-AG08017, and by a grant from the Abercrombie Foundation.
Disclosure: M.A.L. and B.C.L. disclose a financial interest in Scout Diagnostics, a company that recently licensed intellectual property based on studies partially described in this report.
Received September 21, 2007. Accepted in final form February 15, 2008.
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