Regular ArticleLocalization of Neurofibrillary Tangles and Beta-Amyloid Plaques in the Brains of Living Patients With Alzheimer Disease
Section snippets
Preparation of 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2 naphthyl}ethylidene)malononitrile ([18F]FDDNP)
1-(6-methoxy-2-naphthyl)ethanone was subjected to demethylation in boiling hydrochloric acid to give 1-(6-hydroxy-2-naphthyl)ethanone. The Bucherer reaction with 2-(methylamino)ethanol gave 1-{6-[(2-hydroxyethyl)(methyl)amino]-2-naphthyl}ethanone, which, when reacted with malononitrile under the conditions of the Knoevenagel reaction, yielded 2-(1-{6-[(2-hydroxyethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (Figure 1: 3). Reaction of the compound (Figure 1: 3) with
RESULTS
Table 1 summarizes the clinical and demographic information on the two subject groups. Although, on average, patients with AD (n=9) were older and had fewer years of education than control subjects (n=7), these differences were not statistically significant (Age: Wilcoxon-Mann-Whitney statistic=50; exact p=0.33; Education: Wilcoxon Mann-Whitney statistic=71.5; exact p=0.22).
[18F]FDDNP crosses the blood–brain barrier very rapidly in proportion to blood flow, as can be seen in Figure 2, where ROI
DISCUSSION
This work demonstrates, for the first time, the in vivo detection of pathological deposition (i.e., NFTs and APs) in the brain of living AD patients. Earlier attempts to use monoclonal antibodies as probes for in vivo imaging of APs were hampered by their limited ability to cross the blood–brain barrier.33 Congo red, widely used in vitro to label AP, is a charged molecule and lacks sufficient hydrophobicity for diffusion through the blood–brain barrier.34 Chrysamine G enters the blood–brain
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We thank R. Sumida, L. Pan, F. Aguilar (tomographic determinations), D. Dorsey, A. Kaplan, J.L. Cummings and his staff (patient management), B. Amarasekera (cyclotron), D. Stout, and R. Yee (biochemistry). We also thank Dr. Donald Guthrie for his invaluable statistical insight.
This work is supported in part by Department of Energy Grant DE-FC0387-ER60615, the Charles A. Dana Foundation, the Alzheimer's Association Zenith Award, and The Institute for the Study of Aging, Inc.