Gene Tied to Alzheimer's Not Needed by Brain in Surprise Finding

Monday, 11 Aug 2014 05:10 PM

 

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Loss of function of the gene in the brain tied to Alzheimer’s disease may not lead to memory and thinking problems, according to a surprise finding that upends some theories about the disease.

Researchers found that a man with no apolipoprotein E, or APOE, in his body was cognitively normal and showed no other neurological signs of Alzheimer’s, according to a case study published today in the journal JAMA Neurology. Those with a mutation of the gene called APOE4 have a higher risk of developing Alzheimer’s.

More than 5 million Americans have Alzheimer’s disease, the most common form of dementia, and the number is expected to triple by 2050, according to the Alzheimer’s Association. Today’s findings show that APOE isn’t necessary for brain function, a notion that could lead to a new approach for treating the disease, researchers said.

“Minimizing APOE4 levels in the brain may provide us with a new venue for intervention with Alzheimer’s disease and other cognitive disorders,” Mary Malloy, a study author and professor of medicine and pediatrics at the University of California at San Francisco, said in an Aug. 8 telephone interview. “The observations of this patient suggest this strategy can now be entertained seriously. We think the potential harm in minimizing APOE4 levels seems to be nonexistent.”

There are three types of APOE, which helps transport cholesterol, in the body. About 20 percent of people carry APOE4, which is linked to Alzheimer’s, Bruce Miller, a study author and a professor of neurology at UCSF, said in an interview.

Regulating APOE4

“You’re better off having no APOE then APOE4,” he said. “Turning off APOE in the brain, this gives some hope to the idea that we might have very selective ways of down regulating APOE4 in the brain and diminishing its risk for Alzheimer’s.”

In today’s study, a 40-year-old California man was seen at UCSF for severe high cholesterol that wasn’t responsive to treatment. Researchers found he had no APOE in his body, a very rare occurrence, yet he had normal cognitive and eye function, Malloy said.

“We know from other diseases that there are many metabolic process that are very highly redundant that can come in and do a job if one is missing,” she said. “APOE has a purpose but maybe there are ways to get around that. Maybe another protein can take over.”

Joachim Herz, who wrote an accompanying editorial, said now that it’s been shown in humans that a lack of APOE isn’t harmful to the brain, researchers can begin looking for ways to shut off the gene in the brain only.

“This opens the door to explore such possibilities more rigorously because we have the proof of concept that reducing APOE isn’t harmful to patients,” Herz, a professor of molecular genetics, neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas, said today in an interview.


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