{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:18:35Z","timestamp":1767899915852,"version":"3.49.0"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AG029401"],"award-info":[{"award-number":["AG029401"]}]},{"name":"NIH","award":["AG062135"],"award-info":[{"award-number":["AG062135"]}]},{"name":"MKL","award":["AG029401"],"award-info":[{"award-number":["AG029401"]}]},{"name":"MKL","award":["AG062135"],"award-info":[{"award-number":["AG062135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is characterized by a loss of neurons in the cortex and subcortical regions. Previously, we showed that the progressive degeneration of subcortical monoaminergic (MAergic) neurons seen in human AD is recapitulated in the APPswe\/PS1\u0394E9 (APP\/PS) transgenic mouse model. Because degeneration of cholinergic (Ach) neurons is also a prominent feature of AD, we examined the integrity of the Ach system in the APP\/PS model. The overall density of Ach fibers is reduced in APP\/PS1 mice at 12 and 18 months of age but not at 4 months of age. Analysis of basal forebrain Ach neurons shows no loss of Ach neurons in the APP\/PS model. Thus, since MAergic systems show overt cell loss at 18 months of age, the Ach system is less vulnerable to neurodegeneration in the APP\/PS1 model. We also examined whether the proximity to A\u03b2 deposition affected the degeneration of Ach and 5-HT afferents. We found that the areas closer to the edges of compact A\u03b2 deposits exhibit a more severe loss of afferents than the areas that are more distal to A\u03b2 deposits. Collectively, the results indicate that the APP\/PS model recapitulates the degeneration of multiple subcortical neurotransmitter systems, including the Ach system. In addition, the results indicate that A\u03b2 deposits cause global as well as local toxicity to subcortical afferents.<\/jats:p>","DOI":"10.3390\/ijms25095004","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T05:52:02Z","timestamp":1714715522000},"page":"5004","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Loss of Cholinergic and Monoaminergic Afferents in APPswe\/PS1\u0394E9 Transgenic Mouse Model of Cerebral Amyloidosis Preferentially Occurs Near Amyloid Plaques"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-9682","authenticated-orcid":false,"given":"Michael K.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3507-1218","authenticated-orcid":false,"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Personalized Medicine in Brain Disorders, The Guangdong-Hongkong-Macao Joint Laboratory of TCM on Brain-Peripheral Homeostasis and Comprehensive Health, School of Chinese Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0197-4580(02)00057-X","article-title":"Neuron loss in key cholinergic and aminergic nuclei in Alzheimer disease: A meta-analysis","volume":"24","author":"Lyness","year":"2003","journal-title":"Neurobiol. 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