{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:54:20Z","timestamp":1777888460066,"version":"3.51.4"},"reference-count":28,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2016,8,4]],"date-time":"2016-08-04T00:00:00Z","timestamp":1470268800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2016,8,4]]},"abstract":"<jats:p>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\u2019s disease (AD). While the loss of M1-G-protein coupling has been associated with \u03b2-amyloid (A\u03b2) burden in AD, the status of M1 coupling to G-proteins in Parkinson\u2019s disease-related or mixed dementias is unclear.<\/jats:p>\n                  <jats:p>Objective: To test the hypothesis that M1 receptor uncoupling is correlated with A\u03b2 burden, we aimed to study muscarinic M1 neurochemical parameters in neurodegenerative dementias characterized by low and high A\u03b2 loads.<\/jats:p>\n                  <jats:p>Methods: M1 receptors, M1 coupling to G-proteins as well as A\u03b2 were measured in postmortem frontal cortex of a cohort of longitudinally assessed patients with Parkinson\u2019s Disease Dementia (PDD, low A\u03b2 load) and AD with significant subcortical cerebrovascular disease (AD + CVD, high A\u03b2 load).<\/jats:p>\n                  <jats:p>Results: We found unchanged levels of M1 receptors in both dementia groups, while M1 coupling was reduced only in AD + CVD ( p\u200a&lt;\u200a0.01). Furthermore, A\u03b2 concentration was significantly increased only in AD + CVD, and correlated negatively with M1-G-protein coupling in the dementia groups.<\/jats:p>\n                  <jats:p>Conclusions: Our study suggests that loss of M1 coupling to G-proteins may be a neurochemical feature of neurodegenerative dementias with high cortical A\u03b2 burden, and that cholinergic replacement therapies may be more efficacious for PDD due to low A\u03b2 burden.<\/jats:p>","DOI":"10.3233\/jpd-160932","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T11:08:40Z","timestamp":1474369720000},"page":"733-739","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Muscarinic M1 Receptor Coupling to G-protein is Intact in Parkinson\u2019s Disease Dementia"],"prefix":"10.1177","volume":"6","author":[{"given":"Jasinda H.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T.","family":"Francis","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive G.","family":"Ballard","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age-Related Diseases, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Department Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raj N.","family":"Kalaria","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter T.-H.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore"},{"name":"Memory, Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitchell K.P.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore"},{"name":"Wolfson Centre for Age-Related Diseases, King\u2019s College London, London, UK"},{"name":"Memory, Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2010.02.010"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1126\/science.3992249"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1126\/science.7058341"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410290305"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2005.07.010"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.06.001"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2977"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0206-2"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12182"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000187889.17253.b1"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.4.479"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2004.09.019"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07507.x"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900903106"},{"key":"ref017","first-page":"CD006504","volume":"3","author":"Rolinski M","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1177\/1533317511424892"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-307659"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25048"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1993.00540020018011"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3549"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.11.1509"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2013.02.006"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0831-1"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4856-03.2004"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1038\/nn1700"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws173"}],"container-title":["Journal of Parkinson\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-160932","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JPD-160932","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-160932","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:45:37Z","timestamp":1777610737000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JPD-160932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,4]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,8,4]]}},"alternative-id":["10.3233\/JPD-160932"],"URL":"https:\/\/doi.org\/10.3233\/jpd-160932","relation":{},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,4]]}}}