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Sökning: id:"swepub:oai:lup.lub.lu.se:eb952726-1f3b-4ab2-b384-60503a50f9f3" > Data-driven neuropa...

  • Young, Alexandra L.King's College London (författare)

Data-driven neuropathological staging and subtyping of TDP-43 proteinopathies

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • 2023
  • 14 s.

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:eb952726-1f3b-4ab2-b384-60503a50f9f3
  • https://lup.lub.lu.se/record/eb952726-1f3b-4ab2-b384-60503a50f9f3URI
  • https://doi.org/10.1093/brain/awad145DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

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

Anmärkningar

  • TAR DNA-binding protein-43 (TDP-43) accumulation is the primary pathology underlying several neurodegenerative diseases. Charting the progression and heterogeneity of TDP-43 accumulation is necessary to better characterize TDP-43 proteinopathies, but current TDP-43 staging systems are heuristic and assume each syndrome is homogeneous. Here, we use data-driven disease progression modelling to derive a fine-grained empirical staging system for the classification and differentiation of frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP, n = 126), amyotrophic lateral sclerosis (ALS, n = 141) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) with and without Alzheimer’s disease (n = 304). The data-driven staging of ALS and FTLD-TDP complement and extend previously described human-defined staging schema for ALS and behavioural variant frontotemporal dementia. In LATE-NC individuals, progression along data-driven stages was positively associated with age, but negatively associated with age in individuals with FTLD-TDP. Using only regional TDP-43 severity, our data driven model distinguished individuals diagnosed with ALS, FTLD-TDP or LATE-NC with a cross-validated accuracy of 85.9%, with misclassifications associated with mixed pathological diagnosis, age and genetic mutations. Adding age and SuStaIn stage to this model increased accuracy to 92.3%. Our model differentiates LATE-NC from FTLD-TDP, though some overlap was observed between late-stage LATE-NC and early-stage FTLD-TDP. We further tested for the presence of subtypes with distinct regional TDP-43 progression patterns within each diagnostic group, identifying two distinct cortical-predominant and brainstem-predominant subtypes within FTLD-TDP and a further two subcortical-predominant and corticolimbic-predominant subtypes within ALS. The FTLD-TDP subtypes exhibited differing proportions of TDP-43 type, while there was a trend for age differing between ALS subtypes. Interestingly, a negative relationship between age and SuStaIn stage was seen in the brainstem/subcortical-predominant subtype of each proteinopathy. No subtypes were observed for the LATE-NC group, despite aggregating individuals with and without Alzheimer’s disease and a larger sample size for this group. Overall, we provide an empirical pathological TDP-43 staging system for ALS, FTLD-TDP and LATE-NC, which yielded accurate classification. We further demonstrate that there is substantial heterogeneity amongst ALS and FTLD-TDP progression patterns that warrants further investigation in larger cross-cohort studies.

Ämnesord och genrebeteckningar

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

  • Vogel, Jacob W.Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)ja8870vo (författare)
  • Robinson, John L.University of Pennsylvania (författare)
  • McMillan, Corey T.University of Pennsylvania (författare)
  • Ossenkoppele, RikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Amsterdam Neuroscience,Vrije Universiteit Amsterdam(Swepub:lu)ri1513os (författare)
  • Wolk, David A.University of Pennsylvania (författare)
  • Irwin, David J.University of Pennsylvania (författare)
  • Elman, LaurenUniversity of Pennsylvania (författare)
  • Grossman, MurrayUniversity of Pennsylvania (författare)
  • Lee, Virginia M.Y.University of Pennsylvania (författare)
  • Lee, Edward B.University of Pennsylvania (författare)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital(Swepub:lu)mphy-ohn (författare)
  • King's College LondonKlinisk minnesforskning (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Brain146:7, s. 2975-29880006-8950

Internetlänk

Hitta via bibliotek

  • Brain (Sök värdpublikationen i LIBRIS)

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