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

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 92; no. 11; pp. 1206 - 1214
• Main Authors: Alcolea, Daniel, Delaby, Constance, Muñoz, Laia, Torres, Soraya, Estellés, Teresa, Zhu, Nuole, Barroeta, Isabel, Carmona-Iragui, María, Illán-Gala, Ignacio, Santos-Santos, Miguel Ángel, Altuna, Miren, Sala, Isabel, Sánchez-Saudinós, Mª Belén, Videla, Laura, Valldeneu, Sílvia, Subirana, Andrea, Pegueroles, Jordi, Hirtz, Christophe, Vialaret, Jérôme, Lehmann, Sylvain, Karikari, Thomas K, Ashton, Nicholas J, Blennow, Kaj, Zetterberg, Henrik, Belbin, Olivia, Blesa, Rafael, Clarimón, Jordi, Fortea, Juan, Lleó, Alberto
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.11.2021; BMJ Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; amyloid; Amyloid beta-Peptides; Amyloid beta-Peptides - blood; Biomarkers; Biomarkers - blood; Cognitive Dysfunction; Cognitive Dysfunction - blood; Cognitive Dysfunction - diagnosis; csf; Female; Frontotemporal Dementia; Frontotemporal Dementia - blood; Frontotemporal Dementia - diagnosis; Human health and pathology; Humans; Lewy Body Disease; Lewy Body Disease - blood; Lewy Body Disease - diagnosis; Life Sciences; Male; Middle Aged; Neurobiology; Neurodegeneration; Neurofilament Proteins; Neurofilament Proteins - blood; Neurons and Cognition; Neurosciences; Neurovetenskaper; Phosphorylation; Psychiatrics and mental health; tau Proteins; tau Proteins - blood; amyloid; csf; neurodegenerative disease; plasma; biomarker; Alzheimer; CSF
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp-2021-326603

ObjectivesAll 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.MethodsWe 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.ResultsThe 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).ConclusionsPlasma 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.