NEWS OF THE WEEK
Chemical imbalances in Alzheimer's measured A new technique that uses standard magnetic resonance imaging (MRI) equipment to characterize chemical im balances in the brains of Alzheimer's disease patients has been developed by scientists at the Huntington Medical Re search Institutes in Pasadena, Calif. The group's work may lead to a rapid, straightforward diagnostic test for Alz heimer's disease and may be applicable to diagnosing other dementias. Using an MRI version called magnetic resonance spectroscopy (MRS), a team led by MRS unit director Brian D. Ross studied two regions in the brains of 11 elderly Alzheimer's patients and 10 healthy age-matched control subjects. Compared with the controls, the patients showed a 22% increase in myo-inositol— derivatives of which serve as messen gers in cells—and an 11% decrease in N-acetylaspartate, a nerve cell marker. Other research team members included Bruce L. Miller of Harbor Hospital of the University of California, Los Angeles, and Roland Kreis, Rex A. Moats, Truda Shonk, Thomas Ernst, and Suzanne Woolley of the Huntington Institutes. The group's results are published in the May issue of Radiology [187,433 (1993)]. The MRS-based test for Alzheimer's disease takes about 30 minutes, Ross notes. By contrast, current procedures for diagnosing Alzheimer's involve lengthy memory function and neurophysiologies tests that often upset patients and, in any case, don't provide definitive results. Cur rently, only autopsy can confirm the pres ence of Alzheimer's disease. "Physicians have a real need for a test to differentiate Alzheimer's from other dementias to provide the patient and his or her family with a firm diagnosis, and to monitor future protocols for the treat ment of this disease," notes Miller. "We consider this test a major advancement." The new findings also challenge cur rent thinking about the mechanism of Alzheimer's, Ross says. In Alzheimer's disease, neurons that respond to the neurotransmitter acetylcholine—socalled cholinergic neurons—are lost, so researchers have speculated that the dis ease somehow involves disruption of acetylcholine processing in the brain. Many recently developed therapeutic agents for Alzheimer's disease focus on acetylcholine and its receptors. Ross and his coworkers found no 6
MAY 10,1993 C&EN
Ross: test is a major advancement difference between the concentration of acetylcholine precursors in patients in the early or middle stages of Alzhei mer's disease and in control subjects. This suggests acetylcholine is not in volved in these stages of the disease. Use of MRI to study Alzheimer's dis ease was made possible by software called Clinical Proton MRS, which was
developed at the Huntington facilities. This software enables researchers to ex tract spectroscopic information from MRI signals. An automated version of the soft ware, called Proton Brain Examination (PROBE), allows a patient to be tested in only 10 minutes, Ross says. The PROBE software can be used on the 1200 or so General Electric MRI units now in use in the U.S., he adds, and will soon be config ured for other commercial MRI units. The team used MRS to quantify four classes of brain metabolites: N-acetyl residues, phosphorylcholine and glycerophosphorylcholine, myo-inositol, and creatine. The decrease in N-acetyl residues observed in Alzheimer's dis ease patients was not unexpected, Ross says. A decrease of this metabolite is a common pathologic finding in proton magnetic resonance studies of diseases that cause nerve cell loss. The consistent elevation of myo inositol in the brains of Alzheimer's dis ease patients was largely unexpected. The most likely mechanism is inhibition of the enzyme or enzymes responsible for converting myo-inositol to phosphati dyl inositol. This points to disruption of the polyphosphoinositol second-messen ger cascade as a possible cause for the pathology observed in Alzheimer's dis ease, Ross explains. Rudy Baum
Cabinet status for EPA approved by Senate The Senate last week approved pro posed legislation that would elevate the Environmental Protection Agency to a Cabinet-level department. Passed by a vote of 79 to 15, the bill also would abol ish the Council on Environmental Qual ity, as President Bill Clinton requested, and would transfer nearly all of CEO's functions to the new Department of En vironmental Protection. The Senate bill, which has White House backing, now goes to the House of Representatives. That chamber is ex pected to hold a first-cut committee markup session later this month. Making EPA a department with Cabi net status "moves the issue of environ mental protection from the margins of policy-making to the center," says EPA Administrator Carol M. Browner. Brown er would become the first environmental secretary, should Congress make the agency the 15th Cabinet department. As introduced by Sen. John Glenn (D.
Ohio) and retained during committee and floor debates, the Senate bill contains a provision establishing a Bureau of Envi ronmental Statistics within the new de partment. The bureau, analogous to the Bureau of Labor Statistics, would "ana lyze and compile aind publish data neces sary to shape environmental policies," Glenn explains. However, this provision blocked passage of a similar bill in the previous Congress, and may face rough sledding in the House this time around. The Senate bill would give the new department all CEQ functions mandat ed by the 1970 National Environmental Policy Act (ΝΕΡΑ), except that dispute resolution authority would remain with the President. Working through the Bureau of Environmental Statistics, the new department would publish an annual state-of-the-environment report. This report is mandated by ΝΕΡΑ and was issued in the past by CEQ. Lois Ember
