INCREASED LEVELS OF TRUNCATED NERVE GROWTH-FACTOR RECEPTOR IN URINE OF MILDLY DEMENTED PATIENTS WITH ALZHEIMERS-DISEASE

Objective.-In Alzheimer's disease, cholinergic basal forebrain neurons , which have receptors for nerve growth factor (NGF), degenerate, whil e NGF receptors increase in some areas of the neocortex. Levels of the truncated, extracellular portion of the NGF receptor (NGF-Rt) are ele vated 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 pati ents with Alzheimer's disease. Design.-Survey of urine NGF-Rt levels i n neurologically normal (n=19), mildly demented (n=31), and moderately to severely demented (n=31) patients. Setting.-Subjects were particip ants 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 Alzheime r's disease. Aged, non-demented, neurologically normal controls were s elected from the families of the demented subjects. Results.-Urine NGF -Rt levels were substantially elevated in mildly demented patients rel ative to those of non-demented controls. Conclusions.-These results su ggest that an enzyme-linked immunosorbent assay on urine samples may p rovide an antemortem measure of dementia-related neuropathologic chang es, but further study is needed to determine the source and potential clinical utility of increased NGF-Rt levels in urine of mildly demente d patients.