Expression of Trk isoforms in brain regions and in the striatum of patients with Alzheimer's disease

The TrkAII tyrosine kinase receptor differs from the TrkAI isoform by an in sertion of six amino acids in the extracellular domain. We used RT-PCR to d etermine their respective distribution in rat and human brain. Only trkAII transcripts were detected in 12 rat brain regions, while both trkAI and trk AII transcripts were detected in the cerebellum and pituitary gland. In hu man, both trkAI and trkAII transcripts were detected in the frontal, tempor al, and occipital cortex and thalamus, while only trkAI transcripts were de tected in the hippocampus and cerebellum. In the caudate and putamen, trkAI I transcripts were exclusively detected. Thereafter, we studied the express ion of TrkA isoforms in the striatum of five patients with Alzheimer's dise ase (AD), four patients with non-AD dementia, seven patients with Parkinson 's disease, and six paired nondemented elderly control individuals. In cont rols and non-AD patients, a constant expression of trkAII transcripts was d etected within all striatum parts. In AD patients, a heterogeneous decrease in trkAII expression was observed in the caudate, putamen, and ventral str iatum, resulting either in a drop of trkAII transcript levels or in a weak coamplification of trkAII and trkAI transcripts. The alteration of TrkAII g ene expression paralleled those of choline acetyltransferase. Together with previous data, this suggests that the alteration of trk gene expression co uld contribute to a decrease in NGF binding sites and its protective effect s on cholinergic neurons of AD patients. (C) 2000 Academic Press.