Increased muscarinic receptor messenger RNA in Alzheimer's disease temporal cortex demonstrated by in situ hybridization histochemistry.

A 35S-labelled synthetic oligonucleotide directed against part of the mRNA coding for the M1 subtype muscarinic receptor was used for in situ hybridization histochemistry in sections of human temporal cortex. M1 receptor mRNA was found in cell populations throughout the grey matter, especially in pyramidal cells. Quantitative densitometric analysis of autoradiograms was used to compare levels of this mRNA between Alzheimer's disease and controls. A significant (2.7-fold) increase in hybridization signal was found in Alzheimer's disease cases, both in absolute terms and relative to total polyadenylated mRNA as determined by hybridization with an oligodeoxythymidine probe. Elevated levels of muscarinic receptor mRNA may reflect up-regulation of transcription of this gene in response to the cholinergic deficits occurring in the disease.