SwePub
Tyck till om SwePub Sök här!
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Hardy J) ;pers:(Hardy J.);lar1:(umu)"

Search: WFRF:(Hardy J) > Hardy J. > Umeå University

  • Result 1-6 of 6
Sort/group result
   
EnumerationReferenceCoverFind
1.
  •  
2.
  •  
3.
  •  
4.
  • van Rheenen, W, et al. (author)
  • Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
  • 2021
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
  • Journal article (peer-reviewed)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
  •  
5.
  • Hardy, J, et al. (author)
  • Transmitter deficits in Alzheimer's disease.
  • 1985
  • In: Neurochemistry International. - 0197-0186 .- 1872-9754. ; 7:4, s. 545-63
  • Journal article (peer-reviewed)abstract
    • The pattern of neurotransmitter pathway losses in Alzheimer's disease are reviewed. Deficits of the cholinergic pathway from the nucleus basalis, the noradrenergic pathway from the locus coeruleus and the serotoninergic pathway from the raphe nuclei are established. Cortical somatostatin interneurons are affected and dopaminergic neurons may be affected although these may be late or secondary phenomena in the disease process. Other neuronal systems, particularly in the hippocampus and temporal cortex, are also damaged. However, the disease is not one of generalised neuronal atrophy since some neurons are selectively spared. The established pathway-specific losses are discussed in relation to the clinical symptomatology and the pathology of the disorder. The biochemical and histological findings are compared with similar measurements made on tissues from other dementing disorders in an attempt to trace features common to dementias. Finally, as an addendum, a hypothesis is briefly outlined which attempts to explain the common features of the affected neurons and the pathogenesis of the disorder.
  •  
6.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-6 of 6

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view