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Increased Levels of Truncated Nerve Growth Factor Receptor in Urine of Mildly Demented Patients With Alzheimer's Disease
Mark D. Lindner, PhD;
Deidre D. Gordon;
Judith M. Miller;
Pierre N. Tariot, MD;
Keith D. McDaniel, MD;
Robert W. Hamill, MD;
Peter S. DiStefano, PhD;
Rebekah Loy, PhD
Arch Neurol. 1993;50(10):1054-1058.
Abstract
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• Objective.
—In Alzheimer's disease, cholinergic basal forebrain neurons, which have receptors for nerve growth factor (NGF), degenerate, while NGF receptors increase in some areas of the neocortex. Levels of the truncated, extracellular portion of the NGF receptor (NGF-Rt) are elevated in urine of patients with peripheral neuropathies and in animals with peripheral-nerve injury, but it has not been determined whether urine levels of NGF-Rt are altered by the presence and/or progression of dementia-related neuropathologic changes in patients with Alzheimer's disease. In this study, we developed an enzyme-linked immunosorbent assay to determine whether urine levels of NGF-Rt are altered in patients with Alzheimer's disease.
Design.
—Survey of urine NGF-Rt levels in neurologically normal (n=19), mildly demented (n=31), and moderately to severely demented (n=31) patients.
Setting.
—Subjects were participants in the Rochester Alzheimer's Disease Project and mildly demented patients about to begin a clinical drug study.
Patients.
—All patients met established criteria for a clinical diagnosis of probable Alzheimer's disease. Aged, nondemented, neurologically normal controls were selected from the families of the demented subjects.
Results.
—Urine NGF-Rt levels were substantially elevated in mildly demented patients relative to those of nondemented controls.
Conclusions.
—These results suggest that an enzymelinked immunosorbent assay on urine samples may provide an antemortem measure of dementia-related neuropathologic changes, but further study is needed to determine the source and potential clinical utility of increased NGF-Rt levels in urine of mildly demented patients.
Author Affiliations
From the University of Rochester School of Medicine and Dentistry, Neurogerontology Unit (Drs Lindner, McDaniel, Hamill, and Loy and Mss Gordon and Miller) and Psychiatry Unit (Dr Tariot), Monroe Community Hospital, Rochester, NY; Regeneron Pharmaceuticals, Tarrytown, NY (Dr DiStefano); and Canandaigua (NY) Veterans Affairs Medical Center (Dr Loy).
Footnotes
Accepted for publication March 22, 1993.
Reprint requests to Cytotherapeutics, Two Richmond Square, Providence, RI 02906 (Dr Lindner).
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