Increased levels of truncated nerve growth factor receptor in urine of mildly demented patients with Alzheimer's disease
M. D. Lindner, D. D. Gordon, J. M. Miller, P. N. Tariot, K. D. McDaniel, R. W. Hamill, P. S. DiStefano and R. Loy
University of Rochester School of Medicine and Dentistry, Neurogerontology Unit, NY.
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 enzyme-linked 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.
