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  • Spotorno, NicolaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups (författare)

Astrocytic function is associated with both amyloid-β and tau pathology in non-demented APOE 4 carriers

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2022-05-22
  • Oxford University Press (OUP),2022

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:1998d517-bf03-432c-8e34-cfc6ca02f2e8
  • https://lup.lub.lu.se/record/1998d517-bf03-432c-8e34-cfc6ca02f2e8URI
  • https://doi.org/10.1093/braincomms/fcac135DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • A growing body of evidence suggests that astrocytes play a major role in the pathophysiology of Alzheimer's disease. Given that APOE is primarily expressed in astrocytes, these cells might be an important link between the APOE ϵ4 allele and the development of Alzheimer's disease pathology. Here, we investigate this hypothesis in vivo by measuring myo-inositol, a metabolite involved in astrocytic functions, with magnetic resonance spectroscopy. Currently, there is conflicting evidence regarding the relationship between APOE ϵ4 and myo-inositol concentration. Furthermore, data supporting a relationship between APOE ϵ4, myo-inositol and Alzheimer's disease pathology (amyloid-beta and tau proteins) in the preclinical stage of Alzheimer's disease are limited. A previous study revealed differences in myo-inositol levels between APOE ϵ4 carriers and non-carriers already in preclinical Alzheimer's disease participants. However, other reports showed no impact of APOE genotype on the association between myo-inositol and the rate of amyloid-beta accumulation. In the present study, we determined the effect of APOE genotype on the association between myo-inositol and both amyloid-β and tau deposition quantified by PET in 428 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. APOE genotype impacted the associations between myo-inositol and amyloid-β pathology as revealed by an interaction effect between APOE genotype and levels of myo-inositol (P < 0.001) such that higher myo-inositol concentration was related to more amyloid-beta pathology in APOE ϵ4 carriers only. A similar interaction effect was also found when investigating the effect of APOE on the association between myo-inositol and tau pathology (P < 0.01). Focusing on the APOE ϵ4 subsample, myo-inositol partially (17%) mediated the association between amyloid-beta and tau pathology (P < 0.05). Furthermore, in a subgroup of participants with available plasma levels of glial fibrillary acidic protein, a marker of astroglial activation and astrocytosis, we found that glial fibrillary acidic protein correlated with myo-inositol only in APOE e4 carriers (APOE ϵ4 carriers: P < 0.01; APOE ϵ4 non-carriers: P > 0.8), suggesting that myo-inositol might reflect an aspect of the astrocytic involvement in Alzheimer's pathology which is specific to the impact of APOE ϵ4. Therefore, we suggest that myo-inositol is a candidate in vivo marker to study the impact of APOE ϵ4 on the interplay between astrocytes and the pathophysiology of Alzheimer's disease.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Najac, Chlocrossed D.Sign©Leiden University Medical Centre (författare)
  • Stomrud, ErikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-esr (författare)
  • Mattsson-Carlgren, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)med-nmn (författare)
  • Palmqvist, SebastianLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-spa (författare)
  • Van Westen, DanielleLund University,Lunds universitet,Diagnostisk radiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neuroradiologi,Forskargrupper vid Lunds universitet,Diagnostic Radiology, (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Neuroradiology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)ront-dva (författare)
  • Ronen, ItamarLeiden University Medical Centre (författare)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (författare)
  • Klinisk minnesforskningForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Brain Communications: Oxford University Press (OUP)4:32632-1297

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