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This study analyses oligodendrocyte and myelin markers in the frontal WM in a series of AD cases without clinical or pathological co\u2010morbidities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From a consecutive autopsy series, 206 cases had neuropathological changes of AD; among them, only 33 were AD without co\u2010morbidities. WM alterations were first evaluated in coronal sections of the frontal lobe in every case. Then, RT\u2010qPCR and immunohistochemistry were carried out in the frontal WM of AD cases without co\u2010morbidities to analyse the expression of selected oligodendrocyte and myelin markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WM demyelination was more marked in AD with co\u2010morbidities when compared with AD cases without co\u2010morbidities. Regarding the later, mRNA expression levels of<jats:italic>MBP<\/jats:italic>,<jats:italic>PLP1<\/jats:italic>,<jats:italic>CNP<\/jats:italic>,<jats:italic>MAG<\/jats:italic>,<jats:italic>MAL<\/jats:italic>,<jats:italic>MOG<\/jats:italic>and<jats:italic>MOBP<\/jats:italic>were preserved at stages I\u2013II\/0\u2013A when compared with middle\u2010aged (MA) individuals, but significantly decreased at stages III\u2013IV\/0\u2013C. This was accompanied by reduced expression of<jats:italic>NG2<\/jats:italic>and<jats:italic>PDGFRA<\/jats:italic>mRNA, reduced numbers of NG2\u2010, Olig2\u2010 and HDAC2\u2010immunoreactive cells and reduced glucose transporter immunoreactivity. Partial recovery of some of these markers occurred at stages V\u2013VI\/B\u2013C.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present observations demonstrate that co\u2010morbidities have an impact on WM integrity in the elderly and in AD, and that early alterations in oligodendrocytes and transcription of genes linked to myelin proteins in WM occur in AD cases without co\u2010morbidities. These are followed by partial recovery attempts at advanced stages. These observations suggest that oligodendrocytopathy is part of AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12618","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T10:19:00Z","timestamp":1586254740000},"page":"654-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["White matter alterations in Alzheimer\u2019s disease without concomitant pathologies"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"I.","family":"Ferrer","sequence":"first","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics University of Barcelona Barcelona Spain"},{"name":"Bellvitge University Hospital Barcelona Spain"},{"name":"Ministry of Economy and Competitiveness CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases) Institute of Health Carlos III Barcelona 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