The plaques in Alzheimer’s brains consist mostly of an abnormal peptide, or protein fragment, called beta amyloid. This peptide is part of a longer protein called APP (amyloid precursor protein), which abounds in normal brain cells (chart). How does the harmless APP break apart to create the toxic fragment? Researchers deduced more than a decade ago that a pair of protease enzymes–think of them as molecular scissors–were clipping the APP molecule at two locations, which were dubbed the “beta” and “gamma” sites. Those enzymes proved elusive, but one of them has now been collared. Writing in the journal Science last week, the Amgen team positively identified BACE, the enzyme that cleaves APP at the beta site. Its counterpart, GACE, has yet to be identified, but both enzymes seem critical to the formation of plaques. When the researchers deprived cultured cells of BACE, the cells produced less beta amyloid.
The implications are obvious. If a clinical treatment could block the action of BACE, it might well stall the production of plaques –and the progression of Alzheimer’s disease. No one has yet developed such a treatment, but drugmakers are already racing to find one, and the odds seem good. Drugs that inhibit protease enzymes have revolutionized AIDS care in recent years. The new finding suggests that they could help vanquish dementia as well.
How Alzheimer’s begins:
