Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias.

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All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer’s disease (AD) through an easy and minimally invasive approach.We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination.The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A-T- participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1-42/Aβ1-40 (Rho=-0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001).Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach.

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Authors: Daniel Alcolea, Constance Delaby, Laia Muñoz, Soraya Torres, Teresa Estellés, Nuole Zhu, Isabel Barroeta, María Carmona-Iragui, Ignacio Illán-Gala, Miguel Ángel Santos-Santos, Miren Altuna, Isabel Sala, Mª Belén Sánchez-Saudinós, Laura Videla, Sílvia Valldeneu, Andrea Subirana, Jordi Pegueroles, Christophe Hirtz, Jérôme Vialaret, Sylvain Lehmann, Thomas K Karikari, Nicholas J Ashton, Kaj Blennow, Henrik Zetterberg, Olivia Belbin, Rafael Blesa, Jordi Clarimón, Juan Fortea, Alberto Lleó