{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:29:12Z","timestamp":1791239352765,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Uppsala University Hospital"},{"name":"Hans Gabriel and Alice Trolle-Wachtmeister Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were \u226541 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) \u03c4 was observed in the brains of 98% of the 1610 subjects, and amyloid \u03b2-protein (A\u03b2) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects. In 16% of the subjects, HP\u03c4 was limited to the locus coeruleus. In 14 subjects (&lt;1%), no altered proteins were observed. In 3 subjects, only A\u03b2 was observed, and in 17, HP\u03c4 was observed in a distribution other than that seen in ADNC\/PART. The transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant age-related TDP encephalopathy (LATE) was observed in 565 (35%) subjects and \u03b1-synuclein (\u03b1S) pathology, i.e., Lewy body disease (LBD) or multi system atrophy (MSA) was observed in the brains of 21% of the subjects. A total of 39% of subjects with ADNC, 59% of subjects with PART, and 81% of subjects with HP\u03c4 limited to the locus coeruleus lacked concomitant pathologies, i.e., LATE-NC or LBD-NC. Of the 293 (18% of the 1610 subjects) subjects with dementia, 81% exhibited a high or intermediate level of ADNC. In 84% of all individuals with dementia, various degrees of concomitant alterations were observed; i.e., MIXED-NC was a common cause of dementia. A high or intermediate level of PART was observed in 10 subjects with dementia (3%), i.e., tangle-predominant dementia. No subjects exhibited only vascular NC (VNC), but in 17 subjects, severe VNC might have contributed to cognitive decline. Age-related tau astrogliopathy (ARTAG) was observed in 37% of the 1610 subjects and in 53% of those with dementia.<\/jats:p>","DOI":"10.3390\/ijms25074065","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:27:52Z","timestamp":1712305672000},"page":"4065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Ageing-Related Neurodegeneration and Cognitive Decline"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6249-569X","authenticated-orcid":false,"given":"Irina","family":"Alafuzoff","sequence":"first","affiliation":[{"name":"Department of Pathology, Uppsala University Hospital, 751 85 Uppsala, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 05 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-5385","authenticated-orcid":false,"given":"Sylwia","family":"Libard","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uppsala University Hospital, 751 85 Uppsala, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 05 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years","volume":"70","author":"Braak","year":"2011","journal-title":"J. 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