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The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-\u03b2 and phosphorylated-tau pathology at autopsy. To understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimer\u2019s disease, we used a combined post-mortem in situ MRI and histopathology approach. A total of 19 Alzheimer\u2019s disease (10 amnestic and nine non-amnestic) and nine non-neurological control donors underwent 3 T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-\u03b2, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimer\u2019s disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. Exploratory post hoc subgroup analyses indicated that cholinergic cell density could be associated with cortical tract alterations in amnestic Alzheimer\u2019s disease donors only. Our study illustrates that in Alzheimer\u2019s disease, cholinergic degeneration in the nucleus basalis of Meynert may contribute to damaged cortical projections, specifically to the temporal lobe, leading to cognitive deterioration.<\/jats:p>","DOI":"10.1093\/brain\/awac093","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T12:09:08Z","timestamp":1646395748000},"page":"2869-2881","source":"Crossref","is-referenced-by-count":38,"title":["Structural (dys)connectivity associates with cholinergic cell density in Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"145","author":[{"given":"Chen Pei","family":"Lin","sequence":"first","affiliation":[{"name":"Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-2862","authenticated-orcid":false,"given":"Irene","family":"Frigerio","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4922-3286","authenticated-orcid":false,"given":"Baayla D C","family":"Boon","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, location VUmc, Vrije Universiteit Amsterdam, Department of Pathology, Amsterdam Neuroscience , Amsterdam , The Netherlands"},{"name":"Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, Department of Neurology, Alzheimer centrum Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Zhejiang University, College of Biomedical Engineering and Instrument Science , Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke J M","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, location VUmc, Vrije Universiteit Amsterdam, Department of Pathology, Amsterdam Neuroscience , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke H","family":"Bouwman","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Location VUmc, Vrije Universiteit Amsterdam, Department of Neurology, Alzheimer centrum Amsterdam , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-6959","authenticated-orcid":false,"given":"Menno 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