COLOCALIZATION OF HIGH-AFFINITY NEUROTROPHIN RECEPTORS IN NUCLEUS BASALIS OF MEYNERT NEURONS AND THEIR DIFFERENTIAL REDUCTION IN ALZHEIMERS-DISEASE

It has been suggested that degeneration of neurons in Alzheimer's dise ase is the result of diminished trophic support. However, so far no ev idence has been forwarded that neuronal degeneration in Alzheimer's di sease is causally related to insufficient production of neurotrophins. The present study deals with (i) the expression and co-localization o f tyrosine kinase receptors (trks) in the human nucleus basalis of Mey nert and (ii) alterations of these receptors in Alzheimer's disease in the nucleus basalis of Meynert, an area severely affected in Alzheime r's disease. The expression of trkA, trkB and trkC in the nucleus basa lis of Meynert of control and Alzheimer's disease brains was studied u sing three polyclonal antibodies specifically recognizing the extracel lular domain of trkA, trkB and trkC. Brain material of eight controls and seven Alzheimer's disease patients was obtained at autopsy, embedd ed in paraffin and stained immunocytochemically. Using an image analys is system, we determined the proportion of trk neurons expressing the different trk receptors in controls and Alzheimer's disease patients. In control brains, trkA, trkB and trkC were differentially expressed i n numerous nucleus basalis of Meynert neurons. The highest proportion of neurons was found to express trkB (75%), followed by trkC (58%) and trkA (54%). Furthermore, using consecutive sections, a clear co-local ization of trk receptors was observed in the same neurons. The highest degree of co-localization was observed between trkA and trkB. In Alzh eimer's disease patients, the number of immunoreactive neurons and the staining intensity of individual neurons was reduced dramatically. Re duction in the proportion of neurons expressing trkA was 69%, in trkB 47% and in trkC 49%, which indicated a differential reduction in the a mount of trk receptors in Alzheimer's disease. These observations indi cate that nucleus basalis of Meynert neurons can be supported by more than one neurotrophin and that the degeneration of these neurons in Al zheimer's disease is associated with a decreased expression of trk rec eptors, suggesting a decreased neurotrophin responsiveness of nucleus basalis of Meynert neurons in Alzheimer's disease. Copyright (C) 1996 IBRO.