Alterations of muscarinic acetylcholine receptors in atypical Pick's disease without Pick bodies

BACKGROUND: Atypical Pick's disease without Pick bodies is a type of frontotemporal dementia characterised by semantic dementia and temporal dominant lobar atrophy with ubiquitinopathy. No neurochemical analyses have ever been reported in this condition. OBJECTIVE: To investigate muscarinic acetylcholine receptors (mAchR) and their subtypes (M1-M4) in atypical Pick's disease. SUBJECTS: Five cases of atypical Pick's disease were studied. They were compared with nine control cases, 11 cases of Alzheimer's disease, and seven cases of dementia with Lewy bodies. METHODS: A [(3)H]quinuclidinyl benzilate (QNB) binding assay and an immunoprecipitation assay using subtype specific antisera were used. RESULTS: The total amount of mAchR in the temporal cortex was lower in atypical Pick's disease than in controls or Alzheimer's disease cases, but there were no significant differences between the three groups in the frontal cortex. In the temporal cortex, there was a smaller proportion of M1 receptors in atypical Pick's disease than in the controls or in the patients with Alzheimer's disease and dementia with Lewy bodies. In contrast, the proportion of M2 receptor was higher in atypical Pick's disease than in the other three groups. CONCLUSIONS: Depletion of postsynaptic cholinoreceptive neurones in the temporal cortex is more severe in atypical Pick's disease than in other neurodegenerative dementing disorders.