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The 40-year-old man showed up in Dr. Mary Malloy’s clinic with sadly disfiguring symptoms.

His hands, elbows, ears and feet were blemished with protruding pustules and tuber-like welts, some so painful it was hard for him to walk. He suffered from a rare genetic condition called dysbetalipoproteinemia, which caused his cholesterol levels to soar so high that pools of fatty tissue seemed to bubble up under his skin.

But there was something else about this patient. He was missing a gene that, when present in one form, greatly increases the risk of developing Alzheimer’s disease.

Dr. Malloy, who co-directs the Adult Lipid Clinic at the University of California, San Francisco, and her colleagues saw an opportunity to answer an important neurological riddle: Does the absence of the gene — named apolipoprotein E, or APOE, after the protein it encodes — hurt the brain?

If a person with this rare condition were found to be functioning normally, that would suggest support for a new direction in Alzheimer’s treatment.

It would mean that efforts — already being explored by dementia experts — to prevent Alzheimer’s by reducing, eliminating or neutralizing the effects of the most dangerous version of APOE might succeed without causing other problems in the brain.

The researchers, who reported their findings on Monday in the journal JAMA Neurology, discovered exactly that.

They ran a battery of tests, including cognitive assessments, brain imaging and cerebrospinal fluid analyses. The man’s levels of beta-amyloid and tau proteins, which are markers of Alzheimer’s, gave no indication of neurological disease. His brain size was unaffected, and the white matter was healthy. His thinking and memory skills were generally normal.

“This particular case tells us you can actually live without any APOE in the brain,” said Dr. Joachim Herz, a neuroscientist and molecular geneticist at University of Texas Southwestern Medical Center, who was not involved in the research. “So if they were to develop anti-APOE therapies for Alzheimer’s, we would not have to worry about serious neurological side effects.”

Apolipoprotein E, the protein made by the APOE gene, helps transport cholesterol. In the blood, Dr. Malloy said, it guides different proteins containing cholesterol into the liver. In the brain, it chaperones cholesterol from neurons to a storage area while they are changing, she said, and then returns the cholesterol to neurons.

The APOE gene has several forms, and one of them, the APOE4 variant, is the biggest known genetic risk factor for the most common form of Alzheimer’s. People with one copy of APOE4, about 20 percent of the population, have up to five times the risk of developing Alzheimer’s, compared to people without that variant, and they develop the disease earlier.

People with two copies, about 2 percent of the population, have up to 15 times the risk. About 90 percent of people with two copies will develop Alzheimer’s by the time they are age 80.

Another form of the APOE gene, E3, is very common but poses less risk. A third variant, E2, is rare and is the least dangerous.

Dr. Herz, who wrote an editorial about the study, said that the protein made by APOE4 slows the process of clearing beta-amyloid buildup in the brain, leading to the accumulation of the plaques associated with Alzheimer’s.

Proteins made by the other gene variants, APOE3 and APOE2, clear amyloid more quickly, and “in the absence of any APOE, the turnover is fastest,” he said.

So, it makes sense that a person with a fast-clearing form of APOE, or none at all, would have a very low risk of Alzheimer’s. Several experts are working on ways to reduce APOE4 or increase APOE2 in the brain, and the results have been promising.

Dr. Steven Paul, a professor of neuroscience at Weill Cornell Medical College, has found that by using gene therapy to implant mice with APOE2, “we reduced plaque quite effectively and quite quickly,” even in mice that also had APOE4, he said.

Dr. Paul, who is head of research and development at Voyager Therapeutics, said he is now studying the effect in monkeys. “If all goes well, in a year or so we could be thinking seriously about doing this in humans.”

Research led by Dr. David Holtzman, chairman of the neurology department at Washington University School of Medicine in St. Louis, found that when mice with amyloid plaques were given a monoclonal antibody that reduces APOE, the mice developed fewer plaques and cleared some of them from their brains.

Decades ago, before the link to Alzheimer’s was known, reports on a handful of people without APOE suggested that, aside from the physical side effects of astronomical cholesterol levels, they appeared otherwise normal.

But the 40-year-old man, a pipefitter who lives in California’s Central Valley and is married with three children, is the first documented case of an APOE-less person whose brain health has been rigorously tested. He was not further identified to protect his privacy.

“This finding is important,” Dr. Holtzman wrote in an email. It shows “that it is unlikely that APOE is key for normal brain development or function, as there are other proteins that can compensate in its absence.”

The fact that Dr. Malloy’s patient is relatively young makes the results a little less strong, because amyloid accumulation in people destined to get Alzheimer’s may not begin until later in life.

But Dr. Herz said, “based on what we know now, I would say this patient will most likely never accumulate amyloid.”

Dr. Malloy is working to treat the man’s cholesterol problem, which has barely improved despite medication and a healthy diet.

Dr. Paul and others said anti-APOE therapies would have to target broad areas of the brain without crossing the blood-brain barrier and circulating to the liver. They consider that a quite realistic goal.

“Things are developing incredibly rapidly these days,” said Dr. Herz, who is not involved in creating the new therapies. “I’m very confident that we will find approaches that address these issues.”