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Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability

Therriault J, Janelidze S, Benedet AL, Ashton NJ, Arranz Martínez J, Gonzalez-Escalante A, Bellaver B, Alcolea D, Vrillon A, Karim H, Mielke MM, Hyung Hong C, Roh HW, Contador J, Puig Pijoan A, Algeciras-Schimnich A, Vemuri P, Graff-Radford J, Lowe VJ, Karikari TK, Jonaitis E, Brum W, Tissot C, Servaes S, Rahmouni N, Macedo AC, Stevenson J, Fernandez-Arias J, Wang YT, Woo MS, Friese MA, Jia WL, Dumurgier J, Hourregue C, Cognat E, Ferreira PL, Vitali P, Johnson S, Pascoal TA, Gauthier S, Lleó A, Paquet C, Petersen RC, Salmon D, Mattsson-Carlgren N, Palmqvist S, Stomrud E, Galasko D, Son SJ, Zetterberg H, Fortea J, Suárez-Calvet M, Jack CR Jr, Blennow K, Hansson O, Rosa-Neto P.

Resum

Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of disease prevalence in relation to clinical presentation (clinical pretest probability). Here, in a study of 6,896 individuals evaluated from 11 cohort studies from six countries, we determined the positive and negative predictive value of five plasma biomarkers for amyloid-β pathology in cognitively impaired individuals in relation to clinical pretest probability. We observed that p-tau217 could rule in amyloid-β pathology in individuals with probable AD dementia (positive predictive value above 95%). In mild cognitive impairment, p-tau217 interpretation depended on patient age. Negative p-tau217 results could rule out amyloid-β pathology in individuals with non-AD dementia syndromes (negative predictive value between 90% and 99%). Our findings provide a framework for the individual-level interpretation of plasma biomarkers, suggesting that p-tau217 combined with clinical phenotyping can identify patients where amyloid-β pathology can be ruled in or out without the need for PET or CSF confirmatory testing.

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Referència

Therriault J, Janelidze S, Benedet AL, Ashton NJ, Arranz Martínez J, Gonzalez-Escalante A, Bellaver B, Alcolea D, Vrillon A, Karim H, Mielke MM, Hyung Hong C, Roh HW, Contador J, Puig Pijoan A, Algeciras-Schimnich A, Vemuri P, Graff-Radford J, Lowe VJ, Karikari TK, Jonaitis E, Brum W, Tissot C, Servaes S, Rahmouni N, Macedo AC, Stevenson J, Fernandez-Arias J, Wang YT, Woo MS, Friese MA, Jia WL, Dumurgier J, Hourregue C, Cognat E, Ferreira PL, Vitali P, Johnson S, Pascoal TA, Gauthier S, Lleó A, Paquet C, Petersen RC, Salmon D, Mattsson-Carlgren N, Palmqvist S, Stomrud E, Galasko D, Son SJ, Zetterberg H, Fortea J, Suárez-Calvet M, Jack CR Jr, Blennow K, Hansson O, Rosa-Neto P. Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability. Nat Aging. 2024 Nov;4(11):1529-1537. doi: 10.1038/s43587-024-00731-y. Epub 2024 Nov 12. PMID: 39533113; PMCID: PMC11564087.