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Search: WFRF:(Kehoe PG)

  • Result 1-17 of 17
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  • Bellenguez, C, et al. (author)
  • New insights into the genetic etiology of Alzheimer's disease and related dementias
  • 2022
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
  • Journal article (peer-reviewed)abstract
    • Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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  • Norberg, J, et al. (author)
  • Regional differences in effects of APOE ε4 on cognitive impairment in non-demented subjects
  • 2011
  • In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 32:2, s. 135-142
  • Journal article (peer-reviewed)abstract
    • <i>Background:</i> The <i>APOE</i> ε4 allele is a risk factor for Alzheimer’s disease (AD). <i>APOE</i> ε4 is common in non-demented subjects with cognitive impairment. In both healthy people and people with AD, its prevalence has a north-south gradient across Europe. In the present study, we investigated whether the relation between the <i>APOE</i> ε4 allele and cognitive impairment varied across Northern, Middle and Southern Europe. We also investigated whether a north-south gradient existed in subjects with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (MCI) and non-amnestic MCI. <i>Methods:</i> Data from 16 centers across Europe were analyzed. <i>Results:</i> A north-south gradient in <i>APOE</i> ε4 prevalence existed in the total sample (62.7% for <i>APOE</i> ε4 carriers in the northern region, 42.1% in the middle region, and 31.5% in the southern region) and in subjects with SCI and amnestic MCI separately. Only in Middle Europe was the <i>APOE</i> ε4 allele significantly associated with poor performance on tests of delayed recall and learning, as well as with the amnestic subtype of MCI. <i>Conclusion:</i> The <i>APOE</i> ε4 allele frequencies in subjects with SCI and amnestic MCI have a north-south gradient. The relation between the <i>APOE</i> ε4 allele and cognition is region dependent.
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  • Result 1-17 of 17

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