Your browser doesn't support javascript.
loading
Muscarinic M1 Receptor Coupling to G-protein is Intact in Parkinson's Disease Dementia.
Lee, Jasinda H; Francis, Paul T; Ballard, Clive G; Aarsland, Dag; Kalaria, Raj N; Wong, Peter T-H; Chen, Christopher P; Lai, Mitchell K P.
Afiliación
  • Lee JH; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Francis PT; Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
  • Ballard CG; Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
  • Aarsland D; Department Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
  • Kalaria RN; Institute for Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
  • Wong PT; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Chen CP; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
  • Lai MK; Memory, Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore.
J Parkinsons Dis ; 6(4): 733-739, 2016 10 19.
Article en En | MEDLINE | ID: mdl-27662332
BACKGROUND: Postsynaptic cholinergic deficits, including reduced cortical muscarinic M1 receptor coupling to G-proteins, are neurochemical findings postulated to underlie the limited efficacy of presynaptically-targeted cholinergic replacement therapies in Alzheimer's disease (AD). While the loss of M1-G-protein coupling has been associated with ß-amyloid (Aß) burden in AD, the status of M1 coupling to G-proteins in Parkinson's disease-related or mixed dementias is unclear. OBJECTIVE: To test the hypothesis that M1 receptor uncoupling is correlated with Aß burden, we aimed to study muscarinic M1 neurochemical parameters in neurodegenerative dementias characterized by low and high Aß loads. METHODS: M1 receptors, M1 coupling to G-proteins as well as Aß were measured in postmortem frontal cortex of a cohort of longitudinally assessed patients with Parkinson's Disease Dementia (PDD, low Aß load) and AD with significant subcortical cerebrovascular disease (AD + CVD, high Aß load). RESULTS: We found unchanged levels of M1 receptors in both dementia groups, while M1 coupling was reduced only in AD + CVD (p < 0.01). Furthermore, Aß concentration was significantly increased only in AD + CVD, and correlated negatively with M1-G-protein coupling in the dementia groups. CONCLUSIONS: Our study suggests that loss of M1 coupling to G-proteins may be a neurochemical feature of neurodegenerative dementias with high cortical Aß burden, and that cholinergic replacement therapies may be more efficacious for PDD due to low Aß burden.
Asunto(s)
Palabras clave
Buscar en Google
Añadir a Mi BVS
Imprimir
XML
PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteínas de Unión al GTP / Demencia / Receptor Muscarínico M1 / Lóbulo Frontal Tipo de estudio: Observational_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: J Parkinsons Dis Año: 2016 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Países Bajos
Buscar en Google
Añadir a Mi BVS
Imprimir
XML
PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Proteínas de Unión al GTP / Demencia / Receptor Muscarínico M1 / Lóbulo Frontal Tipo de estudio: Observational_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: J Parkinsons Dis Año: 2016 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Países Bajos