Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Mixed Pathologies in a Subject with a Novel PSEN1 G206R Mutation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration. Uppsala Univ Hosp, Dept Surg Pathol, Uppsala, Sweden..ORCID iD: 0000-0003-1043-5385
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.ORCID iD: 0000-0003-3423-2021
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Univ Hlth Network, Krembil Brain Inst, Toronto, ON, Canada.;Univ Toronto, Dept Med, Toronto, ON, Canada.;Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada..ORCID iD: 0000-0001-5466-8370
Show others and affiliations
2022 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 90, no 4, p. 1601-1614Article in journal (Refereed) Published
Abstract [en]

Background: There are more than 300 presenilin-1 (PSEN1) mutations identified but a thorough postmortem neuropathological assessment of the mutation carriers is seldom performed.

Objective: To assess neuropathological changes (NC) in a 73-year-old subject with the novel PSEN1 G206R mutation suffering from cognitive decline in over 20 years. To compare these findings with an age- and gender-matched subject with sporadic Alzheimer's disease (sAD).

Methods: The brains were assessed macro- and microscopically and the proteinopathies were staged according to current recommendations.

Results: The AD neuropathological change (ADNC) was more extensive in the mutation carrier, although both individuals reached a high level of ADNC. The transactive DNA binding protein 43 pathology was at the end-stage in the index subject, a finding not previously described in familial AD. This pathology was moderate in the sAD subject. The PSEN1 G206R subject displayed full-blown alpha-synuclein pathology, while this proteinopathy was absent in the sAD case. Additionally, the mutation carrier displayed pronounced neuroinflammation, not previously described in association with PSEN1 mutations.

Conclusion: Our findings are exceptional, as the PSEN1 G206R subject displayed an end-stage pathology of every common proteinopathy. It is unclear whether the observed alterations are caused by the mutation or are related to a cross-seeding mechanisms. The pronounced neuroinflammation in the index patient can be reactive to the extensive NC or a contributing factor to the proteinopathies. Thorough postmortem neuropathological and genetic assessment of subjects with familial AD is warranted, for further understanding of a dementing illness.

Place, publisher, year, edition, pages
IOS Press, 2022. Vol. 90, no 4, p. 1601-1614
Keywords [en]
Alpha-synuclein, amyloid-beta, cross-seeding, hyperphosphorylated tau, neuroinflammation, PSEN1, TDP43
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-491723DOI: 10.3233/JAD-220655ISI: 000893246500021PubMedID: 36314207OAI: oai:DiVA.org:uu-491723DiVA, id: diva2:1723650
Funder
Hans-Gabriel och Alice Trolle-Wachtmeisters stiftelse för medicinsk forskningAvailable from: 2023-01-03 Created: 2023-01-03 Last updated: 2023-01-03Bibliographically approved

Open Access in DiVA

fulltext(1749 kB)167 downloads
File information
File name FULLTEXT01.pdfFile size 1749 kBChecksum SHA-512
2b4c647df84971f72dfe1c428501ab2c2990420fc3e5fbb090058311aecff6f9fed5cbde69cfab660d9a72e4b43068bad2c69b2c75020c1ad9a19af9403ae22e
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records

Libard, SylwiaGiedraitis, VilmantasKilander, LenaIngelsson, Martin

Search in DiVA

By author/editor
Libard, SylwiaGiedraitis, VilmantasKilander, LenaIngelsson, Martin
By organisation
Neurooncology and neurodegenerationGeriatrics
In the same journal
Journal of Alzheimer's Disease
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 167 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 85 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf