{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:50:26Z","timestamp":1788544226694,"version":"build-2803163510"},"reference-count":104,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,11,8]]},"abstract":"<jats:p>Background: Dysfunction of cholinergic neurotransmission is a hallmark of Alzheimer\u2019s disease (AD); forming the basis for using acetylcholine (ACh) esterase (AChE) inhibitors to mitigate symptoms of ACh deficiency in AD. The Cholinergic Receptor Muscarinic 1 (CHRM1) is highly expressed in brain regions impaired by AD. Previous analyses of postmortem AD brains revealed unaltered CHRM1 mRNA expression compared to normal brains. However, the CHRM1 protein level in AD and other forms of dementia has not been extensively studied. Reduced expression of CHRM1 in AD patients may explain the limited clinical efficacy of AChE inhibitors. Objective: To quantify CHRM1 protein in the postmortem hippocampus and temporal cortex of AD, Parkinson\u2019s disease (PD), and frontotemporal dementia (FTD) patients. Methods: Western blotting was performed on postmortem hippocampus (N\u200a=\u200a19\/73\/7\/9: unaffected\/AD\/FTD\/PD) and temporal cortex (N\u200a=\u200a9\/74\/27: unaffected\/AD\/PD) using a validated anti-CHRM1 antibody. Results: Quantification based on immunoblotting using a validated anti-CHRM1 antibody revealed a significant loss of CHRM1 protein level (&lt;50%) in the hippocampi (78% AD, 66% PD, and 85% FTD) and temporal cortices (56% AD and 42% PD) of dementia patients. Loss of CHRM1 in the temporal cortex was significantly associated with early death (&lt;65\u201375 years) for both AD and PD patients. Conclusion: Severe reduction of CHRM1 in a subset of AD and PD patients can explain the reported low efficacy of AChE inhibitors as a mitigating treatment for dementia patients. Based on this study, it can be suggested that future research should prioritize therapeutic restoration of CHRM1 protein levels in cholinergic neurons.<\/jats:p>","DOI":"10.3233\/jad-220766","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T14:32:49Z","timestamp":1663943569000},"page":"727-747","source":"Crossref","is-referenced-by-count":18,"title":["Loss of Cholinergic Receptor Muscarinic 1 (CHRM1) Protein in the Hippocampus and Temporal Cortex of a Subset of Individuals with Alzheimer\u2019s Disease, Parkinson\u2019s Disease, or Frontotemporal Dementia: Implications for Patient Survival"],"prefix":"10.1177","volume":"90","author":[{"given":"Mohammad Golam","family":"Sabbir","sequence":"first","affiliation":[{"name":"Alzo Biosciences Inc., San Diego, CA, USA"},{"name":"St. Boniface Hospital Albrechtsen Research Centre, Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada"},{"name":"Nova Southeastern University, College of Pharmacy, Fort Lauderdale, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Speth","sequence":"additional","affiliation":[{"name":"Nova Southeastern University, College of Pharmacy, Fort Lauderdale, FL, USA"},{"name":"Department of Pharmacology and Physiology, School of Medicine, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict C.","family":"Albensi","sequence":"additional","affiliation":[{"name":"Nova Southeastern University, College of Pharmacy, Fort Lauderdale, FL, USA"},{"name":"St. Boniface Hospital Albrechtsen Research Centre, Division of Neurodegenerative Disorders, Winnipeg, Manitoba, Canada"},{"name":"University of Manitoba, College of Medicine, Winnipeg, Manitoba, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220766_ref1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41392-019-0063-8","article-title":"History and progress of hypotheses and clinical trials for Alzheimer\u2019s disease","volume":"4","author":"Liu","year":"2019","journal-title":"Signal Transduct Target Ther"},{"key":"10.3233\/JAD-220766_ref2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0022-510X(77)90073-9","article-title":"Neurotransmitter enzyme abnormalities in senile dementia. 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