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.


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.

Publication types

  • Multicenter Study

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides / metabolism
  • Atrophy
  • Biomarkers / cerebrospinal fluid
  • Brain / metabolism
  • Cognitive Dysfunction*
  • Humans
  • tau Proteins / cerebrospinal fluid


  • tau Proteins
  • Amyloid beta-Peptides
  • Biomarkers