Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease

• Published in: Nature communications Vol. 15; no. 1; pp. 2908 - 13
• Main Authors: Gonzalez-Ortiz, Fernando, Kirsebom, Bjørn-Eivind, Contador, José, Tanley, Jordan E., Selnes, Per, Gísladóttir, Berglind, Pålhaugen, Lene, Suhr Hemminghyth, Mathilde, Jarholm, Jonas, Skogseth, Ragnhild, Bråthen, Geir, Grøndtvedt, Gøril, Bjørnerud, Atle, Tecelao, Sandra, Waterloo, Knut, Aarsland, Dag, Fernández-Lebrero, Aida, García-Escobar, Greta, Navalpotro-Gómez, Irene, Turton, Michael, Hesthamar, Agnes, Kac, Przemyslaw R., Nilsson, Johanna, Luchsinger, Jose, Hayden, Kathleen M., Harrison, Peter, Puig-Pijoan, Albert, Zetterberg, Henrik, Hughes, Timothy M., Suárez-Calvet, Marc, Karikari, Thomas K., Fladby, Tormod, Blennow, Kaj
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 59/57; 631/378/1689/1283; 692/53/2422; 692/617/375/132/1283; 82/79; Abnormalities; Alzheimer Disease; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Atrophy; Biomarkers; Biomarkers - cerebrospinal fluid; Blood; Brain; Brain - metabolism; Cerebrospinal fluid; Clinical trials; Cognition; Cognitive ability; Cognitive Dysfunction; Comorbidity; Humanities and Social Sciences; Humans; multidisciplinary; Neurodegeneration; Neurodegenerative diseases; Neurologi; Neurology; Pathology; Pathophysiology; Renal function; Risk factors; Science; Science (multidisciplinary); Tau protein; tau Proteins - cerebrospinal fluid; β-Amyloid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47286-5

Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer’s disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study ( n  = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ (“A”) and neurodegeneration (“N”) abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies. The authors investigated associations of brain-derived-tau (BD-tau) with Aβ pathology, changes in cognition and MRI signatures. Staging Aβ-pathology according to neurodegeneration, using BD-tau, identifies individuals at risk of near-term cognitive decline and atrophy.