Protein clears brain of dementia-causing substance

Amyloid-beta (A-beta) accumulates in the brain as people age, forming tangled plaques that can lead to dementia. Since A-beta is continuously produced in the brain, some mechanism must exist to prevent its build-up, according to Masayoshi Shibata from the University of Southern California in Los Angeles, and associates.

The investigators studied the potential role of three proteins--LRP-1, alpha-2-macroglobulin (a2M), and apolipoprotein E (apoE)--in the clearance of amyloid-beta from the brains of young and adult mice.

When labelled A-beta was injected into the brain, half the protein was cleared within 25.5 minutes, suggesting that a specialised transportation system was moving it out of the brain, the authors report. This transport system lost more than half its effectiveness between infancy and adulthood in the mice.

Moreover, the transport of A-beta fell by 58% when LRP-1 was blocked and by 25% when a2M was blocked, the researchers note. Mice without any ApoE showed a 30% reduction in A-beta removal rates.

Additional studies showed that LRP-1 levels fell substantially as mice aged, but a2M levels remained about the same, the report indicates.

Studies of brains from Alzheimer's disease patients also revealed a shortage of LRP-1, particularly in regions containing A-beta plaques.

The authors conclude that LRP-1, and possibly the other proteins, residing in blood vessels plays an important role in regulating the amount of A-beta in the brain. Shibata's team suggests that a malfunction in this transport system could result in the accumulation of A-beta in the brain.

The researchers propose that actively transporting A-beta out of the brain "may represent a major physiological mechanism that prevents accumulation of A-beta and amyloid deposition in the brain."