SwePub
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:gup.ub.gu.se/309768"
 

Search: onr:"swepub:oai:gup.ub.gu.se/309768" > Association between...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Brockmann, K. (author)

Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson's disease and dementia with Lewy bodies

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-10-30
  • Springer Science and Business Media LLC,2021

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/309768
  • https://gup.ub.gu.se/publication/309768URI
  • https://doi.org/10.1186/s40478-021-01276-6DOI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The clinicopathological heterogeneity in Lewy-body diseases (LBD) highlights the need for pathology-driven biomarkers in-vivo. Misfolded alpha-synuclein (alpha-Syn) is a lead candidate based on its crucial role in disease pathophysiology. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has recently shown high sensitivity and specificity for the detection of misfolded alpha-Syn in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this study we performed the CSF RT-QuIC assay in 236 PD and 49 DLB patients enriched for different genetic forms with mutations in GBA, parkin, PINK1, DJ1, and LRRK2. A subgroup of 100 PD patients was also analysed longitudinally. We correlated kinetic seeding parameters of RT-QuIC with genetic status and CSF protein levels of molecular pathways linked to alpha-Syn proteostasis. Overall, 85% of PD and 86% of DLB patients showed positive RT-QuIC alpha-Syn seeding activity. Seeding profiles were significantly associated with mutation status across the spectrum of genetic LBD. In PD patients, we detected positive alpha-Syn seeding in 93% of patients carrying severe GBA mutations, in 78% with LRRK2 mutations, in 59% carrying heterozygous mutations in recessive genes, and in none of those with bi-allelic mutations in recessive genes. Among PD patients, those with severe GBA mutations showed the highest seeding activity based on RT-QuIC kinetic parameters and the highest proportion of samples with 4 out of 4 positive replicates. In DLB patients, 100% with GBA mutations showed positive alpha-Syn seeding compared to 79% of wildtype DLB. Moreover, we found an association between alpha-Syn seeding activity and reduced CSF levels of proteins linked to alpha-Syn proteostasis, specifically lysosome-associated membrane glycoprotein 2 and neurosecretory protein VGF. These findings highlight the value of alpha-Syn seeding activity as an in-vivo marker of Lewy-body pathology and support its use for patient stratification in clinical trials targeting alpha-Syn.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Quadalti, C. (author)
  • Lerche, S. (author)
  • Rossi, M. (author)
  • Wurster, I. (author)
  • Baiardi, S. (author)
  • Roeben, B. (author)
  • Mammana, A. (author)
  • Zimmermann, M. (author)
  • Hauser, A. K. (author)
  • Deuschle, C. (author)
  • Schulte, C. (author)
  • Waniek, K. (author)
  • Lachmann, I. (author)
  • Sjödin, SimonGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xsjsim (author)
  • Brinkmalm, AnnGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbrian (author)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xbleka (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe (author)
  • Gasser, T. (author)
  • Parchi, P. (author)
  • Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Related titles

  • In:Acta Neuropathologica Communications: Springer Science and Business Media LLC9:12051-5960

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

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