Alzheimer's protein damages blood brain barrier

A protein associated with Alzheimer's disease causes damage to the blood vessels in the brain, leading to a leaky blood brain barrier and increased risk of neurodegenerative...
20 May 2012


A protein associated with Alzheimer's disease causes damage to the blood vessels of the brain, ultimately leading to a leaky blood brain barrier and an increased risk of neurodegenerative disease.  Identifying this mechanism offers new targets for treating and even preventing disease.

Amyloid beta plaquesAPOE4 is one of three common forms of human apolipoprotein E, and is a major genetic risk factor for Alzheimer's disease, as well as being associated with poor recovery from brain injury.  Now, research published in the journal Nature shows that APOE4 activates a pro-inflammatory pathway in pericytes, cells found in the walls of brain capillaries and responsible for regulating blood flow and controlling the blood brain barrier.    Activation of the pathway leads to increased uptake of toxins in the brain essentially by introducing a leak to the blood brain barrier.

The blood brain barrier plays an essential role in allowing nutrients in and keeping toxins out of the brain, and dysfunction of this barrier can lead to damage and ultimately neurodegenerative disease, including the build up of beta amylase plaques that are characteristic of Alzheimer's.

Robert Bell from the University of Rochester in New York, and colleagues, targeted a particular component of this pathway, cyclophilin A.  This is a protein which is inhibited by other forms of APOE, and is known to be involved in blood vessel damage elsewhere in the body, being implicated in heart disease as well as Alzheimer's.  Mice carrying the ApoE4 gene express 5 times more cyclophilin A than those carrying the other versions of the ApoE gene.

Blocking cyclophilin A in mice, either genetically or using the immune suppressant drug cyclosporine, reversed the damage and dramatically cut the leakiness of brain blood vessels.  This offers a good target for treating or preventing the damage that can ultimately lead to Alzheimer's, the most common cause of dementia in older adults.


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