APOE4 carriers show early breakdown to blood-brain barrier, before cognitive impairment

Contributed by Daniel Nation, PhD, UCI MIND Faculty Member, Associate Professor of Psychological Science at UCI
APOE4 is the strongest known genetic risk factor for Alzheimer’s disease, the most common cause of dementia characterized by the accumulation of amyloid plaques and tau tangles. Although the predominant view has been that APOE4 conveys risk for Alzheimer’s dementia primarily through its effects on amyloid levels, prior work has also shown that APOE4 has adverse effects on the blood vessels of the brain.
In a recent study published in Nature, colleagues at University of Southern California and I demonstrated that APOE4 carriers show early breakdown in the blood-brain barrier on brain imaging and an increase in cerebral spinal fluid markers of pericyte (a cell that wraps around blood vessels) injury and blood vessel inflammation. The blood-brain barrier breakdown and pericyte injury were observed at a very early disease stage, when patients were still cognitively unimpaired, and further damage was observed in patients with cognitive impairment. Increased pericyte injury was also predictive of future cognitive decline. Careful examination of brain imaging and cerebral spinal fluid markers showed that blood-brain barrier breakdown occurred independent of amyloid and tau.
These findings point to potential new pathways for early detection and intervention for Alzheimer’s disease. You can read more about this study on Alzforum.
About Daniel Nation, PhD:
Daniel Nation, PhD is an Associate Professor of Psychological Science in the UCI School of Social Ecology. He earned his PhD in clinical health psychology from the University of Miami. He completed a postdoctoral fellowship researching biological psychiatry and neuroscience at UC San Diego and another postdoctoral fellowship studying cognitive rehabilitation in traumatic brain injury at the VA San Diego Healthcare System. Dr. Nation’s research examines the role of vascular factors in cognitive aging with an aim to improve early detection and identify targets for potential new therapies.