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Coomans, Emma M.Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam,Amsterdam Neuroscience
(författare)
Interactions between vascular burden and amyloid-β pathology on trajectories of tau accumulation
- Artikel/kapitelEngelska2024
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:f45d877d-f2f2-4584-8cdd-67e3a77de257
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https://lup.lub.lu.se/record/f45d877d-f2f2-4584-8cdd-67e3a77de257URI
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https://doi.org/10.1093/brain/awad317DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Cerebrovascular pathology often co-exists with Alzheimer’s disease pathology and can contribute to Alzheimer’s disease-related clinical progression. However, the degree to which vascular burden contributes to Alzheimer’s disease pathological progression is still unclear. This study aimed to investigate interactions between vascular burden and amyloid-β pathology on both baseline tau tangle load and longitudinal tau accumulation. We included 1229 participants from the Swedish BioFINDER-2 Study, including cognitively unimpaired and impaired participants with and without biomarker-confirmed amyloid-β pathology. All underwent baseline tau-PET (18F-RO948), and a subset (n = 677) underwent longitudinal tau-PET after 2.5 ± 1.0 years. Tau-PET uptake was computed for a temporal meta-region-of-interest. We focused on four main vascular imaging features and risk factors: microbleeds; white matter lesion volume; stroke-related events (infarcts, lacunes and haemorrhages); and the Framingham Heart Study Cardiovascular Disease risk score. To validate our in vivo results, we examined 1610 autopsy cases from an Arizona-based neuropathology cohort on three main vascular pathological features: cerebral amyloid angiopathy; white matter rarefaction; and infarcts. For the in vivo cohort, primary analyses included age-, sex- and APOE ε4-corrected linear mixed models between tau-PET (outcome) and interactions between time, amyloid-β and each vascular feature (predictors). For the neuropathology cohort, age-, sex- and APOE ε4-corrected linear models between tau tangle density (outcome) and an interaction between plaque density and each vascular feature (predictors) were performed. In cognitively unimpaired individuals, we observed a significant interaction between microbleeds and amyloid-β pathology on greater baseline tau load (β = 0.68, P < 0.001) and longitudinal tau accumulation (β = 0.11, P < 0.001). For white matter lesion volume, we did not observe a significant independent interaction effect with amyloid-β on tau after accounting for microbleeds. In cognitively unimpaired individuals, we further found that stroke-related events showed a significant negative interaction with amyloid-β on longitudinal tau (β = −0.08, P < 0.001). In cognitively impaired individuals, there were no significant interaction effects between cerebrovascular and amyloid-β pathology at all. In the neuropathology dataset, the in vivo observed interaction effects between cerebral amyloid angiopathy and plaque density (β = 0.38, P < 0.001) and between infarcts and plaque density (β = −0.11, P = 0.005) on tau tangle density were replicated. To conclude, we demonstrated that cerebrovascular pathology—in the presence of amyloid-β pathology—modifies tau accumulation in early stages of Alzheimer’s disease. More specifically, the co-occurrence of microbleeds and amyloid-β pathology was associated with greater accumulation of tau aggregates during early disease stages. This opens the possibility that interventions targeting microbleeds may attenuate the rate of tau accumulation in Alzheimer’s disease.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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van Westen, DanielleLund University,Lunds universitet,Diagnostisk radiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neuroradiologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Diagnostic Radiology, (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Neuroradiology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)ront-dva
(författare)
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Binette, Alexa PichetLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)al1314pi
(författare)
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Strandberg, OlofLund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,MR Physics,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups(Swepub:lu)teor-osn
(författare)
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Spotorno, NicolaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)ni1407sp
(författare)
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Serrano, Geidy E.Banner Sun Health Research Institute
(författare)
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Beach, Thomas G.Banner Sun Health Research Institute
(författare)
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Palmqvist, SebastianLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital(Swepub:lu)med-spa
(författare)
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Stomrud, ErikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital(Swepub:lu)med-esr
(författare)
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Ossenkoppele, RikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Vrije Universiteit Amsterdam,Amsterdam Neuroscience,Skåne University Hospital(Swepub:lu)ri1513os
(författare)
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Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital(Swepub:lu)mphy-ohn
(författare)
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Klinisk minnesforskningForskargrupper vid Lunds universitet
(creator_code:org_t)
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Ingår i:Brain147:3, s. 949-9600006-8950
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Coomans, Emma M.
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van Westen, Dani ...
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Strandberg, Olof
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Spotorno, Nicola
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Serrano, Geidy E ...
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Beach, Thomas G.
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Palmqvist, Sebas ...
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Hansson, Oskar
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