Rik Ossenkoppele, Gemma Salvadó, Shorena Janelidze, Alexa Pichet Binette, Divya Bali, Linda Karlsson, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Erik Stomrud, Joseph Therriault, Nesrine Rahmouni, Pedro Rosa-Neto, Emma M Coomans, Elsmarieke van de Giessen, Wiesje M van der Flier, Charlotte E Teunissen, Erin M Jonaitis, Sterling C Johnson, Sylvia Villeneuve, Tammie L S Benzinger, Suzanne E Schindler, Randall J Bateman, James D Doecke, Vincent Doré, Azadeh Feizpour, Colin L Masters, Christopher Rowe, Heather J Wiste, Ronald C Petersen, Clifford R Jack, Oskar Hansson
{"title":"血浆p-tau217和tau-PET预测认知功能未受损个体的未来认知能力下降：对临床试验的影响","authors":"Rik Ossenkoppele, Gemma Salvadó, Shorena Janelidze, Alexa Pichet Binette, Divya Bali, Linda Karlsson, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Erik Stomrud, Joseph Therriault, Nesrine Rahmouni, Pedro Rosa-Neto, Emma M Coomans, Elsmarieke van de Giessen, Wiesje M van der Flier, Charlotte E Teunissen, Erin M Jonaitis, Sterling C Johnson, Sylvia Villeneuve, Tammie L S Benzinger, Suzanne E Schindler, Randall J Bateman, James D Doecke, Vincent Doré, Azadeh Feizpour, Colin L Masters, Christopher Rowe, Heather J Wiste, Ronald C Petersen, Clifford R Jack, Oskar Hansson","doi":"10.1038/s43587-025-00835-z","DOIUrl":null,"url":null,"abstract":"<p><p>Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R<sup>2</sup><sub>PET</sub> = 0.34 versus R<sup>2</sup><sub>plasma</sub> = 0.33, P<sub>difference</sub> = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)<sub>PET</sub> = 1.61 (1.48-1.76) versus HR<sub>plasma</sub> = 1.57 (1.43-1.72), P<sub>difference</sub> = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R<sup>2</sup> = 0.35, P < 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. Thus, plasma p-tau217 and tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use enhances screening efficiency for preclinical AD trials.</p>","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":" ","pages":"883-896"},"PeriodicalIF":17.0000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092243/pdf/","citationCount":"0","resultStr":"{\"title\":\"Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials.\",\"authors\":\"Rik Ossenkoppele, Gemma Salvadó, Shorena Janelidze, Alexa Pichet Binette, Divya Bali, Linda Karlsson, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Erik Stomrud, Joseph Therriault, Nesrine Rahmouni, Pedro Rosa-Neto, Emma M Coomans, Elsmarieke van de Giessen, Wiesje M van der Flier, Charlotte E Teunissen, Erin M Jonaitis, Sterling C Johnson, Sylvia Villeneuve, Tammie L S Benzinger, Suzanne E Schindler, Randall J Bateman, James D Doecke, Vincent Doré, Azadeh Feizpour, Colin L Masters, Christopher Rowe, Heather J Wiste, Ronald C Petersen, Clifford R Jack, Oskar Hansson\",\"doi\":\"10.1038/s43587-025-00835-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R<sup>2</sup><sub>PET</sub> = 0.34 versus R<sup>2</sup><sub>plasma</sub> = 0.33, P<sub>difference</sub> = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)<sub>PET</sub> = 1.61 (1.48-1.76) versus HR<sub>plasma</sub> = 1.57 (1.43-1.72), P<sub>difference</sub> = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R<sup>2</sup> = 0.35, P < 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. 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引用次数: 0
摘要
血浆p-tau217和tau正电子发射断层扫描（PET）是阿尔茨海默病（AD）强有力的预后生物标志物，但它们在预测认知功能未受损（CU）个体未来认知能力下降方面的相对表现尚不清楚。在一项包括9个队列和1474名个体的头对头比较研究中，我们发现血浆p-tau217和内侧颞叶tau-PET信号与全球认知综合测试中的认知能力下降（R2PET = 0.34 vs R2plasma = 0.33， p差= 0.653）和进展为轻度认知障碍(风险比（HR）PET = 1.61 （1.48-1.76) vs HRplasma = 1.57 (1.43-1.72)， p差= 0.322）有相似的关联。血浆和PET联合模型优于单一生物标志物模型(R2 = 0.35， P
Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials.
Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R2PET = 0.34 versus R2plasma = 0.33, Pdifference = 0.653) and with progression to mild cognitive impairment (hazard ratio (HR)PET = 1.61 (1.48-1.76) versus HRplasma = 1.57 (1.43-1.72), Pdifference = 0.322). Combined plasma and PET models were superior to the single-biomarker models (R2 = 0.35, P < 0.01). Sequential selection using plasma phosphorylated tau at threonine 217 (p-tau217) and then tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 76% reduction when using plasma p-tau217 alone. Thus, plasma p-tau217 and tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use enhances screening efficiency for preclinical AD trials.
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