Glutamate(NMDA) receptor NR1 subunit mRNA expression in Alzheimer's disease

We analyzed the expression profile of two NMDAR1 mRNA isoform subsets. NR1( 0xx) and NR1(1xx), in discrete regions of human cerebral cortex. The subset s are characterized by the absence or presence of a 21-amino acid N-termina l cassette. Reverse transcription polymerase chain reaction for NR1 isoform s was performed on total RNA preparations from spared and susceptible regio ns from 10 pathologically confirmed Alzheimer's disease (AD) cases and 10 m atched controls. Primers spanning the splice insert yielded two bands, 342 bp (NR1(0xx)) and 405 bp (NR1(1xx)), on agarose gel electrophoresis. The ba nds were visualized with ethidium and quantified by densitometry. NR1(1xx) transcript expression was calculated as a proportion of the NR1(1xx) + NR1( 0xx) total. Values were significantly lower in AD cases than in controls in mid-cingulate cortex, p < 0.01, superior temporal cortex, p < 0.01 and hip pocampus, p similar to 0.05. Cortical proportionate NR1(1xx) transcript exp ression was invariant over the range of ages acid areas of controls tested, at similar to 50%. This was also true for AD motor and occipital cortex. P roportionate NR1(1xx) expression in AD cingulate and temporal cortex was lo wer at younger ages and increased with age: this regression was significant ly different from that in the homotropic areas of controls. Variations in N R1 N-terminal cassette expression may underlie the local vulnerability to e xcitotoxic damage of some areas in the AD brain. Alternatively, changes in NR1 mRNA expression may arise as a consequence of the AD disease process.