Enzyme inhibition key to Alzheimer's?

Enzyme inhibition key to Alzheimer's?

Some scientists have suggested that an abnormal gene codes for the overproduction of amyloid protein in patients with Alzheimer's disease. But the excessive amyloid deposition so characteristic of the disease may actually be the result of too little breakdown, rather than too much production, according to three independent studies reported this week.

Nearly two dozen scientists report in the Feb. 11 NATURE that a newly discovered protein precursor for Alzheimer-associated amyloid also contains a structure similar to known inhibitors of certain enzymes. Because these so-called serine protease enzymes are needed to digest proteins, their inhibition might lead to excessive protein accumulation in tissues-and perhaps to the amyloid deposition found in the brains of Alzheimer's patients, say the scientists.

Researchers at California Biotechnology, Inc., in Mountain View and at Mount Sinai School of Medicine in New York City screened a library of human-brain genetic material and found a gene that codes for the new amyloid precursor and its "inhibitor" insert. At the same time, two other groups-one at Asahi Chemical Industry Co. Ltd. in Shizuoka, Japan, and the other at Harvard Medical School and Children's Hospital in Boston and at the University of Massachusetts Medical Center in Worcester - discovered the gene in both normal and Alzheimer brain tissue.

The Massachusetts group also has isolated the gene on the chromosome linked to Down syndrome, another condition associated with amyloid deposition in the brain. Understanding the clinical implications of the new gene, however, will require more studies, say the scientists.

How abnormal amyloid deposition occurs and whether it is a cause or a result of Alzheimer's is controversial (SN:9/19/87,p.181). Although Rachael L. Neve of Children's Hospital acknowledged in an interview that "the jury's still out" on the exact role of amyloid in Alzheimer's, she thinks it is not abnormal amyloid production involved, but something abnormal happening to the amyloid after it is produced. Since completing the reported study, she and her co-workers have made genetic probes that distinguish between the two forms of amyloid (with and without the built-in inhibitor), and have gotten what Neve calls "exciting" preliminary results on the distribution of different amyloids in tissues.