INCREASED MESSENGER-RNA EXPRESSION OF THE 695 AND 751 AMINO-ACID ISOFORMS OF THE BETA-AMYLOID PROTEIN-PRECURSOR IN THE THALAMUS OF 17-YEAR-OLD CYNOMOLGUS (MACACA-FASCICULARIS) MONKEYS

The levels of expression of messenger RNAs of the 695 and 751 amino ac id isoforms of the beta-amyloid protein precursor in the brains of thr ee-year-old and 17-year-old cynomolgus monkeys (Macaca fascicularis) w ere visualized and quantified by in situ hybridization histochemistry using S-35-labelled oligonucleotide probes. The analysis was carried o ut on coronal brain sections taken through the hippocampus and thalamu s at the level of the geniculate nuclei. High densities of beta-amyloi d protein precursor(695) and beta-amyloid protein precursor(751) messe nger RNAs were found in the medial aspects of the mediodorsal, centrom edian and parafascicular nuclei of the 17-year-old monkeys. The messen ger RNA levels of the 695 and 751 isoforms were about two- and seven-f old, respectively, those found in the same nuclei of the three-year-ol d animals. The levels of these messenger RNA transcripts in the 17-yea r-old monkeys were not significantly different from those in the three -year-old animals in other brain areas e.g. the temporal cortex, entor hinal cortex and hippocampus. No Alzheimer's disease-like neuropatholo gy in terms of diffuse or senile beta-amyloid plaques, dystrophic neur ites or neurofibrillary tangles were detectable by specific innumohist ochemical procedures in the above thalamic nuclei of the 17-year-old a nimals. In addition no reactive gliosis was seen in the thalamus of th ese monkeys. The presence of increased levels of beta-amyloid protein precursor(695) and beta-amyloid protein precursor(751) messenger RNAs and the absence of any Alzheimer's disease-like pathology in the thala mus of the middle-aged monkeys may suggest that enhanced transcription of the beta-amyloid protein precursor gene may precede by many years any manifestation of the beta-amyloid protein accumulation/deposition. The data obtained in the thalamus of the 17-year-old monkeys may be i ndicative of early molecular events associated with the aging process.