Blood-Brain Barrier Permeability Linked to Alzheimer's Disease Pathophysiology

Strategic Insights -

New research suggests that cerebrovascular disease influences Alzheimer's disease risk and progression, with permeability of the blood-brain barrier playing a critical role in the development of the condition. A study conducted by researchers from Columbia University found that biomarker concentrations of vascular endothelial growth factor (VEGF) family members were associated with Alzheimer's disease plasma biomarker concentrations, as well as MRI markers of cerebrovascular disease. The findings suggest that blood-brain barrier dysfunction contributes to cerebrovascular lesions observed on MRI and is associated with neuroinflammation in middle age.

Key Takeaways:

  • The study included 488 middle-aged participants from the Offspring Study of Racial and Ethnic Disparities in AD who had MRI and plasma biomarker data available.
  • Higher placental growth factor (PlGF) levels were associated with older age, greater white matter hyperintensity (WMH) volume, and higher levels of glial fibrillary acidic protein (GFAP), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL).
  • Higher VEGF-D levels were associated with increased GFAP and NfL levels, while basic fibroblast growth factor (bFGF) concentration was associated with a lower Ab42/40 ratio and higher p-tau181 levels.
  • The best fitting path model showed that PlGF had an indirect effect on GFAP levels mediated by WMH, and GFAP subsequently had a direct positive effect on p-tau181, which in turn had a positive effect on NfL levels.
  • VEGF-D and bFGF levels also had a positive direct effect on NfL levels.
  • The findings suggest that permeability of the blood-brain barrier is linked to Alzheimer's disease pathophysiology and contributes to cerebrovascular lesions observed on MRI in middle age.

Statistics:

  • 488 participants were included in the study, with a mean age of 54.3 (SD = 10.5) and 66.8% women.
  • Higher PlGF levels were associated with an increase in WMH volume of 0.2 (CI: 0.11-0.29).
  • Higher VEGF-D levels were associated with an increase in GFAP levels of 0.11 (CI: 0.02-0.19).
  • The study found significant bivariate relationships between WMH, Ab42/Ab40 ratio, p-tau181, GFAP, and NfL with VEGF biomarkers.

Sources:

  • NewsRx. Study Findings on Vascular Diseases and Conditions Are Outlined in Reports from Columbia University (Alzheimer Disease, Vascular Disease, and Blood-Brain Barrier Permeability Biomarkers in Middle-Aged Adults). Cardiovascular Week. October 20, 2025; p 906.
  • Alzheimer Disease, Vascular Disease, and Blood-Brain Barrier Permeability Biomarkers in Middle-Aged Adults. Neurology, 2025;105(9).
  • Lippincott Williams & Wilkins, Two Commerce Sq, 2001 Market St, Philadelphia, PA 19103, USA (publisher of Neurology)
  • Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (research institution)