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Disease progression...
Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology
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- Mastenbroek, Sophie E. (author)
- Lund 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
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- Vogel, Jacob W. (author)
- Lund University,Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Neurodegenerativ forskning,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,LU Profile Area: Proactive Ageing,Lund University Profile areas,Neurodegenerative research,Department of Clinical Sciences, Malmö,Faculty of Medicine
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- Collij, Lyduine E. (author)
- Lund 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
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- Serrano, Geidy E. (author)
- Banner Sun Health Research Institute
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- Tremblay, Cécilia (author)
- Banner Sun Health Research Institute
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- Young, Alexandra L. (author)
- King's College London
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- Arce, Richard A. (author)
- Banner Sun Health Research Institute
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- Shill, Holly A. (author)
- Barrow Neurological Institute, Phoenix
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- Driver-Dunckley, Erika D. (author)
- Mayo Clinic Scottsdale-Phoenix, Arizona
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- Mehta, Shyamal H. (author)
- Mayo Clinic Scottsdale-Phoenix, Arizona
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- Belden, Christine M. (author)
- Banner Sun Health Research Institute
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- Atri, Alireza (author)
- Brigham and Women's Hospital / Harvard Medical School,Banner Sun Health Research Institute
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- Choudhury, Parichita (author)
- Banner Sun Health Research Institute
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- Barkhof, Frederik (author)
- University College London,Amsterdam Neuroscience,Vrije Universiteit Amsterdam
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- Adler, Charles H. (author)
- Mayo Clinic Scottsdale-Phoenix, Arizona
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- Ossenkoppele, Rik (author)
- Lund 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,Amsterdam Neuroscience,Vrije Universiteit Amsterdam
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- Beach, Thomas G. (author)
- Banner Sun Health Research Institute
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- Hansson, Oskar (author)
- Lund 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
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Nature Communications. - 2041-1723. ; 15:1
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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Abstract
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- Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer’s disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
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Mastenbroek, Sop ...
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Vogel, Jacob W.
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Collij, Lyduine ...
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Serrano, Geidy E ...
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Tremblay, Cécili ...
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Young, Alexandra ...
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show more...
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Arce, Richard A.
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Shill, Holly A.
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Driver-Dunckley, ...
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Mehta, Shyamal H ...
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Belden, Christin ...
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Atri, Alireza
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Choudhury, Paric ...
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Barkhof, Frederi ...
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Adler, Charles H ...
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Ossenkoppele, Ri ...
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Beach, Thomas G.
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Hansson, Oskar
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- MEDICAL AND HEALTH SCIENCES
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Lund University