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Cited by 87Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

Step by step: towards a better understanding of the genetic architecture of Alzheimer’s disease

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Lambert, Jean-Charles, Ramirez, Alfredo, Grenier-Boley, Benjamin, Bellenguez, Céline·2023·Molecular Psychiatry
DOI 10.1038/s41380-023-02076-1PMC PMC10615767
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Abstract

Alzheimer’s disease (AD) is considered to have a large genetic component. Our knowledge of this component has progressed over the last 10 years, thanks notably to the advent of genome-wide association studies and the establishment of large consortia that make it possible to analyze hundreds of thousands of cases and controls. The characterization of dozens of chromosomal regions associated with the risk of developing AD and (in some loci) the causal genes responsible for the observed disease signal has confirmed the involvement of major pathophysiological pathways (such as amyloid precursor protein metabolism) and opened up new perspectives (such as the central role of microglia and inflammation). Furthermore, large-scale sequencing projects are starting to reveal the major impact of rare variants – even in genes like APOE – on the AD risk. This increasingly comprehensive knowledge is now being disseminated through translational research; in particular, the development of genetic risk/polygenic risk scores is helping to identify the subpopulations more at risk or less at risk of developing AD. Although it is difficult to assess the efforts still needed to comprehensively characterize the genetic component of AD, several lines of research can be improved or initiated. Ultimately, genetics (in combination with other biomarkers) might help to redefine the boundaries and relationships between various neurodegenerative diseases.

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Authors
Lambert, J.-C., Ramirez, A., Grenier-Boley, B., & Bellenguez, C.
Affiliations
Inserm (FR)
Corresponding author
Lambert, Jean-Charles
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2023-05-02
Volume
28
Issue
7
Pages
2716-2727
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-023-02076-1
PMC
PMC10615767
OpenAlex
W4367677543
Cited by
87
References
191
Citations by year
2026: 24 · 2025: 27 · 2024: 31 · 2023: 5
FWCI
3.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DZNE Pub (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • LillOA (Université de Lille (University Of Lille)) (submittedVersion, other-oa)
Funders
  • Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease
  • Agence Nationale de la Recherche (ANR-11-LABX-0009)
  • Institut National de la Santé et de la Recherche Médicale
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
Alzheimer's disease, genetic architecture, genetic susceptibility loci, APP processing, microglia, neuroinflammation, rare variants, apolipoprotein E, polygenic risk score, genome-wide association study, neurodegenerative diseases, biomarkers
MeSH terms
Alzheimer Disease, Apolipoproteins E, Humans, Risk Factors, Biomarkers, Genome-Wide Association Study

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