Normal cognition is observed in a patient without apolipoprotein E, risk factor for Alzheimer's

A 40-year-old California man exhibits normal cognitive function although he has no apolipoprotein E (apoE), which has been believed to be important for brain function. A mutation of apoE, however, is also a known risk factor for Alzheimer disease (AD). Researchers suggest this could mean that therapies to reduce apoE in the central nervous system may one day help treat neurodegenerative disorders such as AD. The study was authored by Angel C. Y. Mak, PhD, of the University of California, San Francisco, (UCSF) and colleagues, and published online in JAMA Neurology.

The patient was referred to UCSF with severe high cholesterol that was relatively unresponsive to treatment. He has a rare form of severe dysbetalipoproteinemia (abnormally high levels of cholesterol and triglycerides in the blood), and the authors identified a mutation leading to his apoE deficiency.

Extensive studies of the patient's retinal and neurocognitive function were performed because apoE is found in the central nervous system and the retinal pigment epithelium. The results: Despite lacking apoE, the patient had normal vision and exhibited normal cognitive, neurological, and eye function. The patient also had normal brain imaging findings and normal cerebrospinal fluid levels of other proteins.

“Failure of detailed neurocognitive and retinal studies to demonstrate defects in our patient suggests either that the functions of apoE in the brain and eye are not critical or that they can be fulfilled by a surrogate protein,” say the authors. “Surprisingly, with respect to central nervous system function, it appears that having no apoE is better than having the apoE4 protein. Thus, projected therapies aimed at reducing apoE4 in the brain could be of benefit in neurodegenerative disorders such as Alzheimer disease.” Read the article.