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Ageing-Related Neurodegeneration and Cognitive Decline
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala Univ Hosp, Dept Pathol, S-75185 Uppsala, Sweden..ORCID-id: 0000-0002-6249-569x
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi och neurodegeneration. Uppsala Univ Hosp, Dept Pathol, S-75185 Uppsala, Sweden..ORCID-id: 0000-0003-1043-5385
2024 (Engelska)Ingår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, nr 7, artikel-id 4065Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 ≥ 41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid β-protein (Aβ) 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, HPτ was limited to the locus coeruleus. In 14 subjects (<1%), no altered proteins were observed. In 3 subjects, only Aβ was observed, and in 17, HPτ 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 α-synuclein (αS) 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 HPτ 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.

Ort, förlag, år, upplaga, sidor
MDPI, 2024. Vol. 25, nr 7, artikel-id 4065
Nyckelord [en]
ageing, hyperphosphorylated-tau, amyloid beta-protein, alpha-synuclein, transactive DNA-binding protein 43, PART, ADNC, LATE, LBD/PD, ARTAG
Nationell ämneskategori
Neurologi Gerontologi, medicinsk/hälsovetenskaplig inriktning Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-528144DOI: 10.3390/ijms25074065ISI: 001201569700001PubMedID: 38612875OAI: oai:DiVA.org:uu-528144DiVA, id: diva2:1860297
Tillgänglig från: 2024-05-23 Skapad: 2024-05-23 Senast uppdaterad: 2024-05-23Bibliografiskt granskad

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Alafuzoff, IrinaLibard, Sylwia
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Institutionen för immunologi, genetik och patologiNeuroonkologi och neurodegeneration
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