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

Department of Psychiatry, Yokohama City University School of Medicine, Yokohama, Japan.
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 5.58). 08/2003; 74(7):965-7.
Source: PubMed

ABSTRACT 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.
To investigate muscarinic acetylcholine receptors (mAchR) and their subtypes (M1-M4) in atypical Pick's disease.
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.
A [(3)H]quinuclidinyl benzilate (QNB) binding assay and an immunoprecipitation assay using subtype specific antisera were used.
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.
Depletion of postsynaptic cholinoreceptive neurones in the temporal cortex is more severe in atypical Pick's disease than in other neurodegenerative dementing disorders.

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    ABSTRACT: There are no US FDA-approved therapies for the management of frontotemporal dementia (FTD). Evidence-based medicine that would support a FDA indication for the treatment of FTD requires large-scale, randomized, double-blind, placebo-controlled trials that do not currently exist. Progress in obtaining approval and therapeutic indications for FTD has been severely hampered by the heterogeneity of clinical and pathological phenotypes seen in various FTD disease states. These issues are often misinterpreted by clinicians, caregivers and patients suggesting that potential treatment options are nonexistent for this devastating disease. This article discusses these issues in the context of recent studies and publications investigating therapeutic options in FTD, and further suggests a rationale for individualized therapy in FTD. Targeting the myriad of symptoms seen in FTD requires recognition of such symptoms that may play primary or secondary roles in the spectrum of deficits that lead to functional disability in FTD, and the availability of a wide range of therapeutic options that may be helpful in alleviating such symptomatology. Fortunately, agents targeting the many cognitive, behavioral, psychiatric and motor symptoms that can be seen in FTD are readily available, having been previously developed and approved for symptomatic benefit in other disease states. In contrast to the widespread belief that beneficial treatments are not available for FTD today, our therapeutic armament is stocked with pharmacological tools that may improve quality of life for those suffering from this devastating and incurable class of degenerative diseases.
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