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Perturbations in the brain lysosomal system, including the cathepsin family of proteases, have been implicated in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> where they may be involved in proteolytic clearance of misfolded and abnormally aggregated peptides. However, the status of cathepsin D (catD) is unclear in Lewy body dementia, the second most common form of neurodegenerative dementia after <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>, and characterized by Lewy bodies (<jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content>) containing aggregated \u03b1\u2010synuclein. Furthermore, earlier reports of catD changes in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> have not been entirely consistent. We measured CatD immunoreactivities in the temporal (Brodmann area <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>21) and parietal (<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>40) cortices of well characterized <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> brains as well as two clinical subtypes of Lewy body dementia, namely Parkinson disease dementia (<jats:styled-content style=\"fixed-case\">PDD<\/jats:styled-content>) and dementia with Lewy bodies (<jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>), known to show varying degrees of concomitant <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> pathology. Increased catD immunoreactivities in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> were found for both neocortical regions measured, where they also correlated with neuropathological <jats:styled-content style=\"fixed-case\">NFT<\/jats:styled-content> scores and phosphorylated <jats:styled-content style=\"fixed-case\">pS<\/jats:styled-content>er396 tau burden, and appeared to co\u2010localize at least partly to <jats:styled-content style=\"fixed-case\">NFT<\/jats:styled-content>\u2010containing neurons. In contrast, catD was increased only in <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>40 in <jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content> and not at all in <jats:styled-content style=\"fixed-case\">PDD<\/jats:styled-content>, did not correlate with <jats:styled-content style=\"fixed-case\">LB<\/jats:styled-content> scores, and did not appreciably co\u2010localize with \u03b1\u2010synuclein inclusions. Our study suggests that catD upregulation may be an adaptive response to <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>\u2010related processes leading to neurofibrillary degeneration, but may not be directly associated with formation of \u03b1\u2010synuclein inclusions in Lewy body dementia.<\/jats:p>","DOI":"10.1111\/bpa.12631","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T08:44:18Z","timestamp":1532681058000},"page":"63-74","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Lysosomal cathepsin D is upregulated in Alzheimer's disease neocortex and may be a marker for neurofibrillary degeneration"],"prefix":"10.1111","volume":"29","author":[{"given":"Yuek Ling","family":"Chai","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce R.","family":"Chong","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaju","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Howlett","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Halsey","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasinda H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore Kent Ridge Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Attems","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Campus for Ageing and Vitality Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Department NVS Center for Alzheimer Research Division for Neurogeriatrics Karolinska Institute Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Francis","sequence":"additional","affiliation":[{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7685-1424","authenticated-orcid":false,"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":"Memory Aging and Cognition Centre National University Health System Kent Ridge Singapore"},{"name":"Wolfson Centre for Age\u2010Related Diseases King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.3.387"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000165917"},{"key":"e_1_2_12_4_1","unstructured":"ADI(2010)World Alzheimer report 2010: the global economic impact of dementia. 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