Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease
Fernando González‐Ortiz, Bjørn‐Eivind Kirsebom, José Contador, Jordan E. Tanley, Per Selnes, Berglind Gísladóttir, Lene Pålhaugen, Mathilde Suhr Hemminghyth, Jonas Alexander Jarholm, Ragnhild Eide Skogseth, Geir Bråthen, Gøril Grøndtvedt, Atle Bjørnerud, Sandra Tecelão, Knut Waterloo, Dag Aarsland, Aida Fernández‐Lebrero, Greta García‐Escobar, Irene Navalpotro‐Gómez, Michael Turton, Agnes Hesthamar, Przemysław R. Kac, Johanna Nilsson, José A. Luchsinger, Kathleen M. Hayden, Peter Harrison, Albert Puig‐Pijoan, Henrik Zetterberg, Timothy M. Hughes, Marc Suárez‐Calvet, Thomas K. Karikari, Tormod Fladby, Kaj Blennow
Abstract
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.