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<p>Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer’s disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (<i>n</i> = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma eMTBR-tau243 showed strong associations with tau positron emission tomography binding (<i>β</i> = 0.72, <i>R</i><sup>2</sup> = 0.56) and cognitive performance (<i>β</i> = 0.60, <i>R</i><sup>2</sup> = 0.40), outperforming other plasma tau (%p-tau217 and %p-tau205) biomarkers. These results suggest that plasma eMTBR-tau243 may be useful for estimating the tauopathy load in AD, thereby improving the diagnostic evaluation of AD in clinical practice and monitoring the efficacy of tau-targeted therapies in clinical trials.</p>

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Plasma MTBR-tau243 biomarker identifies tau tangle pathology in Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月31日

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  • Kanta Horie,
  • Gemma Salvadó,
  • Rama K. Koppisetti,
  • Shorena Janelidze,
  • Nicolas R. Barthélemy,
  • Yingxin He,
  • Chihiro Sato,
  • Brian A. Gordon,
  • Hong Jiang,
  • Tammie L. S. Benzinger,
  • Erik Stomrud,
  • David M. Holtzman,
  • Niklas Mattsson-Carlgren,
  • John C. Morris,
  • Sebastian Palmqvist,
  • Rik Ossenkoppele,
  • Suzanne E. Schindler,
  • Oskar Hansson,
  • Randall J. Bateman

摘要

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer’s disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma eMTBR-tau243 showed strong associations with tau positron emission tomography binding (β = 0.72, R2 = 0.56) and cognitive performance (β = 0.60, R2 = 0.40), outperforming other plasma tau (%p-tau217 and %p-tau205) biomarkers. These results suggest that plasma eMTBR-tau243 may be useful for estimating the tauopathy load in AD, thereby improving the diagnostic evaluation of AD in clinical practice and monitoring the efficacy of tau-targeted therapies in clinical trials.