Association between the LRP1B and APOE loci and the development of Parkinson’s disease dementia

Output Details

Preprint May 25, 2022

Published May 24, 2022

Parkinson's disease (PD) is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of PD, particularly in the later stages of the disease. However, the rate of cognitive decline varies widely among PD patients, and the genetic basis for this heterogeneity is incompletely understood. Here, we have analysed 3,964 clinically diagnosed PD cases to explore the genetic factors associated with rate of progression to PD dementia. Genome-wide survival analysis identified the APOE-ϵ4 allele as a major risk factor for the conversion to PD dementia, as well as three new loci, including the ApoE and APP receptor LRP1B. Biomarker analysis also implicates the amyloid pathway in PD dementia, suggesting that amyloid-targeting therapy may have an important role in preventing PDD.
Identifier (DOI)
10.1093/brain/awac414
Tags
  • APOE (Apolipoprotein E)
  • Cognitive dysfunction/dementia
  • Genetic susceptibility
  • LRP1B
  • Original Research
  • Parkinson's disease

Meet the Authors

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    Raquel Real, PhD

    Key Personnel: Team Hardy

    University College London

  • Alejandro Martínez Carrasco, MSc

    Key Personnel: Team Hardy

    University College London

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    Michael Lawton

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    Manuela Tan

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    Maryam Shoai, PhD

    Key Personnel: Team Hardy

    University College London

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    Jean-Christophe Corvol

  • Mina Ryten

    Co-PI (Core Leadership): Team Hardy Team Wood

    University College London

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    Catherine Bresner

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    Leon Hubbard

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    Alexis Brice

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    Fanny Artaud

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    Nigel Williams

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    Michele Hu

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    Ben-Shlomo Yoav

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    Donald Grosset

  • John Hardy, PhD

    Lead PI (Core Leadership): Team Hardy

    University College London

  • Huw Morris

    Collaborating PI: Team Hardy

    University College London