Research suggests that reducing or neutralizing one variety of the APOE gene would not harm the brain, while making Alzheimer’s less likely.
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.”
Based on the current rates of success in creating new drugs for Alzheimer’s disease, it could take 260 years until the next one is approved, according to an analysis led by a Massachusetts Institute of Technology economist.
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