ApoE4 influence on Alzheimer’s progression

Nov 22, 2023

The ApoE4 gene variant may accelerate tau pathology at lower amyloid levels in Alzheimer’s disease, influencing disease progression and treatment strategies​​.

November 2023 – JAMA Neurology


Key takeaways


  • ApoE4 and tau pathology: Individuals carrying the ApoE4 gene variant exhibit more rapid spreading of tau pathology, a hallmark of Alzheimer’s disease, even when amyloid levels, another key Alzheimer’s biomarker, are lower. This suggests a distinct disease progression pattern in ApoE4 carriers
  • Early onset and progression in ApoE4 carriers: The accelerated tau spreading in those with the ApoE4 variant may lead to earlier onset of Alzheimer’s symptoms and a faster decline in cognitive functions. This has significant implications for early diagnosis and management of the disease in these individuals
  • Targeted Alzheimer’s therapy insights: The study’s insights into the interaction between ApoE4 and tau pathology could guide the development of more personalised treatment strategies. By understanding how ApoE4 affects tau spreading, researchers can design therapies that specifically target these mechanisms


These findings highlight the critical role of genetics, particularly the ApoE4 variant, in age-related neurodegenerative diseases like Alzheimer’s. This enhances our understanding of how genetic predispositions influence disease development and progression, which is crucial for developing preventative strategies in ageing populations.


Read the article at: Steward A, Biel D, Dewenter A, et al. ApoE4 and Connectivity-Mediated Spreading of Tau Pathology at Lower Amyloid Levels. JAMA Neurol. Published online November 06, 2023. doi:10.1001/jamaneurol.2023.4038