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From Mental Illness Research, Education, and Clinical Center and Departments of Psychiatry and Behavioral Sciences (G.L., J.B.L., M.A.R., E.R.P.), Department of Pathology (I.S., J.Z., T.J.M.), and Geriatric Research, Education, and Clinical Center and Department of Medicine (G.D.S.), VA Puget Sound Health Care System, University of Washington, Seattle; Department of Neurology (J.F.Q., J.A.K.), Oregon Health and Science University and Portland VA Medical Center, Portland; and Biosource Division of Invitrogen (M.B.), Camarillo, CA.
Address correspondence and reprint requests to Dr. Thomas J. Montine, Department of Pathology, University of Washington, Harborview Medical Center, 300 9th Ave., Seattle, WA 98104 tmontine{at}u.washington.edu
Background: Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and Aß42 as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD.
Methods: We determined the ratio of CSF tau/Aß42 (T/Aß) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12).
Results: We identified 16% of the control group with abnormally elevated CSF T/Aß; all were 53 years or older. Using age-matched controls with normal CSF T/Aß we showed that the high CSF T/Aß subgroup of controls had significantly increased frequency of the 
4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture.
Conclusions: These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease.
Supported by grants from the NIH: AG05136 and AG08017.
Disclosure: Dr. Brodey is an employee of Biosource Division of Invitrogen. None of the other authors has reported conflicts of interest.
Received September 29, 2006. Accepted in final form March 14, 2007.
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