Alzheimer’s disease is the most common cause of dementia in older adults. Brain changes associated with the disease include abnormal clumps (amyloid-β plaques) and tangled bundles of fibers (tau tangles). It’s thought that these changes eventually cause the death of nerve cells, leading to a progressive decline in memory and thinking skills.

But amyloid-β and tau are likely not the only drivers of Alzheimer’s dementia. Recent studies suggest that breakdown of the blood-brain barrier may also play a role. The blood-brain barrier is a protective, tightly packed mix of cells that sits between the blood vessels that lead to the brain and the brain tissue itself.

People with a variation of the gene apolipoprotein E (APOE), called APOE4, have an increased risk of developing Alzheimer’s dementia, often at an earlier age. APOE4 is known to contribute to amyloid-β and tau accumulation. A research team led by Drs. Axel Montagne and Berislav Zlokovic from the University of Southern California wanted to know if APOE4 also affects the blood-brain barrier.

The study was funded in part by NIH’s National Institute on Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS). Results were published on May 7, 2020, in Nature.


Our findings suggest that breakdown of the blood-brain barrier contributes to the cognitive decline associated with APOE4 and may be a target for the development of preventive or therapeutic drugs for people who carry this gene variation.
Berislav Zlokovic


Read Full Article