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

Staging amyloid-beta (A beta) 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 A beta 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 A beta ("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 A beta-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-A beta therapies. The authors investigated associations of brain-derived-tau (BD-tau) with A beta pathology, changes in cognition and MRI signatures. Staging A beta-pathology according to neurodegeneration, using BD-tau, identifies individuals at risk of near-term cognitive decline and atrophy.