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Sökning: WFRF:(De Deyn P. P.) > Karolinska Institutet

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  • Bellenguez, C, et al. (författare)
  • New insights into the genetic etiology of Alzheimer's disease and related dementias
  • 2022
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
  • Tidskriftsartikel (refereegranskat)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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  • Visser, P. J., et al. (författare)
  • Development of screening guidelines and clinical criteria for predementia Alzheimer's disease
  • 2008
  • Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 30:4, s. 254-265
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. Methods: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2 - 3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. Results: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.
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