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  • Groot, ColinLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam (author)

Phospho-tau with subthreshold tau-PET predicts increased tau accumulation rates in amyloid-positive individuals

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2022-09-09
  • Oxford University Press (OUP),2023
  • 12 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:5a940936-7c7b-4573-82fe-1fa8c581daf7
  • https://lup.lub.lu.se/record/5a940936-7c7b-4573-82fe-1fa8c581daf7URI
  • https://doi.org/10.1093/brain/awac329DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

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

Notes

  • Different tau biomarkers become abnormal at different stages of Alzheimer's disease, with CSF phospho-tau typically becoming elevated at subthreshold levels of tau-PET binding. To capitalize on the temporal order of tau biomarker-abnormality and capture the earliest changes of tau accumulation, we implemented an observational study design to examine longitudinal changes in Tau-PET, cortical thickness and cognitive decline in amyloid-β-positive (A+) individuals with elevated CSF P-tau levels (P+) but subthreshold Tau-PET retention (T-). To this end, individuals without dementia (i.e., cognitively unimpaired or mild cognitive impairment, N = 231) were selected from the BioFINDER-2 study. Amyloid-β-positive (A+) individuals were categorized into biomarker groups based on cut-offs for abnormal CSF P-tau217 and [18F]RO948 (Tau) PET, yielding groups of tau-concordant-negative (A + P-T-; n = 30), tau-discordant (i.e., A + P+T-; n = 48) and tau-concordant-positive (A + P+T+; n = 18) individuals. In addition, 135 amyloid-β-negative, tau-negative, cognitively unimpaired individuals served as controls. Differences in annual change in regional Tau-PET, cortical thickness and cognition between the groups were assessed using general linear models, adjusted for age, sex, clinical diagnosis and (for cognitive measures only) education. Mean follow-up time was ∼2 years. Longitudinal increase in Tau-PET was faster in the A + P+T- group than in the control and A + P-T- groups across medial temporal and neocortical regions, with the highest accumulation rates in the medial temporal lobe. The A + P+T- group showed a slower rate of increases in tau-PET compared to the A + P+T+ group, primarily in neocortical regions. We did not detect differences in yearly change in cortical thickness or in cognitive decline between the A + P+T- and A + P-T- groups. The A + P+T+ group, however, showed faster cognitive decline compared to all other groups. Altogether, these findings suggest that the A + P+T- biomarker profile in persons without dementia is associated with an isolated effect on increased Tau-PET accumulation rates but not on cortical thinning and cognitive decline. While this suggests that the tau-discordant biomarker profile is not strongly associated with short-term clinical decline, this group does represent an interesting population for monitoring effects of interventions with disease modifying agents on tau accumulation in early Alzheimer's disease, and for examining the emergence of tau aggregates in Alzheimer's disease. Further, we suggest to update the AT(N) criteria for Alzheimer's disease biomarker classification to APT(N).

Subject headings and genre

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

  • Smith, RubenLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Regeneration in Movement Disorders,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-rsm (author)
  • 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 (author)
  • Binette, Alexa PichetLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)al1314pi (author)
  • Leuzy, AntoineLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)an3415le (author)
  • Wuestefeld, AnikaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)an8567wu (author)
  • Wisse, Laura E MLund University,Lunds universitet,Diagnostisk radiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Diagnostic Radiology, (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)la3343wi (author)
  • 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 (author)
  • Mattsson-Carlgren, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-nmn (author)
  • Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)nkir-sje (author)
  • Strandberg, OlofLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,MR Physics,Clinical Memory Research,Lund University Research Groups(Swepub:lu)teor-osn (author)
  • Ossenkoppele, RikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam(Swepub:lu)ri1513os (author)
  • 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 (author)
  • Klinisk minnesforskningForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Brain : a journal of neurology: Oxford University Press (OUP)146:4, s. 1580-15911460-2156
  • In:Brain: Oxford University Press (OUP)146:4, s. 1580-15910006-8950

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