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Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology

Mastenbroek, Sophie E. LU ; Vogel, Jacob W. LU ; Collij, Lyduine E. LU ; Serrano, Geidy E. ; Tremblay, Cécilia ; Young, Alexandra L. LU ; Arce, Richard A. ; Shill, Holly A. ; Driver-Dunckley, Erika D. and Mehta, Shyamal H. , et al. (2024) In Nature Communications 15(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
5133
publisher
Nature Publishing Group
external identifiers
  • scopus:85196043808
  • pmid:38879548
ISSN
2041-1723
DOI
10.1038/s41467-024-49402-x
language
English
LU publication?
yes
id
b240b66d-66e7-4929-b090-1833efb4456c
date added to LUP
2024-07-03 11:37:54
date last changed
2024-07-03 14:16:43
@article{b240b66d-66e7-4929-b090-1833efb4456c,
  abstract     = {{<p>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.</p>}},
  author       = {{Mastenbroek, Sophie E. and Vogel, Jacob W. and Collij, Lyduine E. and Serrano, Geidy E. and Tremblay, Cécilia and Young, Alexandra L. and Arce, Richard A. and Shill, Holly A. and Driver-Dunckley, Erika D. and Mehta, Shyamal H. and Belden, Christine M. and Atri, Alireza and Choudhury, Parichita and Barkhof, Frederik and Adler, Charles H. and Ossenkoppele, Rik and Beach, Thomas G. and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-49402-x}},
  doi          = {{10.1038/s41467-024-49402-x}},
  volume       = {{15}},
  year         = {{2024}},
}