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

González Ortiz, Fernando; Contador, Jose; Fernández-Lebrero, Aida; Navalpotro-Gómez, Irene; Suárez-Calvet, Marc; Blennow, Kaj

doi:http://dx.doi.org/10.1038/s41467-024-47286-5

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

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Gonzalez-Ortiz F, Kirsebom BE, Contador J, Tanley JE, Selnes P, Gísladóttir B, et al. Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease. Nat Commun. 2024 Apr 4;15(1):2908. DOI: 10.1038/s41467-024-47286-5

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.