DECREASED TRKA NEUROTROPHIN RECEPTOR EXPRESSION IN THE PARIETAL CORTEX OF PATIENTS WITH ALZHEIMERS-DISEASE

The cholinergic neurons of the basal forebrain system are sensitive to nerve growth factor (NGF), a member of the neurotrophin gene family. Since the cholinergic system is affected early in the course of Alzhei mer's disease (AD), it was hypothesized that a deficit in NGF, e.g. re duced neurotrophin uptake by specific receptors, may play a role in ne uronal cell death in AD. We quantitated mRNA levels of neurotrophins ( NGF, BDNF, NT-3, NT-4/5) and their receptors (trkA, trkB, trkC, p75) i n AD postmortem parietal cortex (n = 16) and cerebellum (n = II). We a pplied highly sensitive reverse transcription-polymerase chain reactio n (RT-PCR) in rapid autopsy derived brain tissue (mean postmortem dela y 147 +/- 96 min., n = 53) to minimize postmortem mRNA variations. In the AD parietal cortex trkA mRNA levels were more than two times lower as compared to controls (n = 16, mean, SEM 0.26 +/- 0.07 units/S12, r ange, 0-1.78, and n = 11, 0.59 +/-: 0.10 units/S12, range, 0.17-1.10, respectively, P = 0.015). TrkA mRNA levels did not appear to be altere d in the AD cerebellum as compared to normal human cerebellum. NGF, BD NF, NT-3, NT-4/5, as well as trkB, trkC and p75 mRNA levels were uncha nged in AD parietal cortex and cerebellum as compared to controls. Thi s finding suggests that a reduced expression of the trkA receptor may contribute to impaired NGF-trkA signalling and a reduced transport of NGF in cholinergic neurons. These results reveal a central specific ro le of the high affinity NGF receptor during neurodegeneration in AD. ( C) 1998 Elsevier Science Ireland Ltd.