One team, two clues in Alzheimer's puzzle.

Collaboration between clinical and basic researchers in Boston has yielded two findings that should help physicians, scientists, and patients fight Alzheimer's disease. Their work may explain how a chemical in the brain, apolipoprotein E, can increase a person's risk of developing Alzheimer's disease (SN: 8/13/94, p.111). Other results suggest that these researchers have devised a simple diagnostic test for the disorder.

Like everyone else involved in the treatment or study of this dementia, Huntington Potter of Harvard Medical School in Boston has long sought an easy, certain way to diagnose Alzheimer's, a disease characterized by progressive loss of memory and other brain functions. Currently, researchers depend on a battery of neurological and psychological tests that can be confirmed only by examining the patient's brain after death.

Now, preliminary results indicate that monitoring pupil dilation after exposure to a chemical commonly used by eye doctors may one day accomplish just that, Potter says.

Because of similarities between Alzheimer's disease and Down's syndrome, Potter had combed the scientific literature for unusual traits in Down's patients that people with Alzheimer's might share. As early as 1959, others had noticed that Down's patients react strongly to chemicals that block transmission of the nervous system messenger acetylcholine: Their pupils dilate and their heart rates increase more than normal.

Leondard F.M. Scinto, now at Brigham and Women's Hospital in Boston, tried one such chemical, tropicamide, on 58 individuals. Of those 58, 14 were already diagnosed as having Alzheimer's, 5 were suspected of having Alzheimer's, 4 suffered from other dementias, 3 showed some loss of mental function, and 32 had scored well on the initial screening tests of brain function.

Each participant first watched television in a dimly lit, quiet room for a few minutes. A researcher measured the viewer's pupils, then administered a drop of sterile water into one eye and a drop of tropicamide into the other. The researcher did not know which drop was which. For the next hour, a special infrared video camera monitored changes in the pupils.

The eyes of Alzheimer's patients and people suspected of having the disease reacted similarly to the eyes of the three volunteers with some loss of mental function, Scinto, Potter, and their colleagues report. This reaction differed most from that of healthy individuals one-half hour into the test, the group reports in the Nov. 11 SCIENCE.

Pupils dilate about 5 percent in normal individuals and in those with other types of dementia but 23 percent in those with or possibly suffering from Alzheimer's. This test pointed to Alzheimer's in 18 of the 19 people having or believed to have this disease, the researchers note.

Furthermore, pupils seem to become sensitive to tropicamide very early in the course of the disease. A man with slightly abnormal brain function who had tested positive for Alzheimer's now shows signs of being in the early stages of the disease, Potter says.

"[The test] is very provocative if it holds true," comments Zaven S. Khachaturian of the National Institute on Aging in Bethesda, Md. He adds, however, that the test must be studied in many more people to determine whether it holds up in different types of people with different types of Alzheimer's.

Even Potter cautions against physicians trying this test out yet. "[It] requires rather specialized equipment," he warns. "You can't just use an eyedropper and ruler."

In the second study, reported in the Nov. 3 NATURE, Potter's group demonstrated that the cholesterol-carrying molecule apolipoprotein E (apo E) promotes the formation of deposits, called amyloid plaques, in the brain. These plaques serve as a hallmark of Alzheimer's disease.

Apo E-IV, the version of the molecule associated with increased risk of Alzheimer's, stimulates plaque formation the most, while apo E-III works less well, and apo E-II can even slow plaque formation, the team reports. These findings agree with those of earlier epidemiological studies (SN: 1/1/94, p.8).

The researchers had already established that the protein ACT helps stimulate the creation of filaments, which clump into amyloid plaques. These new experiments, done by mixing high concentrations of the substances involved in a test tube, demonstrate that ACT links with one part of the amyloid fragment and apo E with another part. Other studies indicate that ACT and apo E are more abundant in the parts of the brain most affected by Alzheimer's, Potter notes.

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