15 Oct Apolipoprotein E Research May Open New Door to Alzheimer Research

MedicalResearch.comInterview with:
Mary Malloy, M.D.
Co-director of the Adult Lipid Clinic and the director of the Pediatric Lipid Clinic
UCSF Medical Center

Medical Research: What are the main findings of the study?

Dr. Malloy: We studied an individual whom we found to be homozygous for a rare loss of function mutation in apolipoprotein E.

Because apolipoprotein E is necessary for clearance of lipoproteins from plasma, he has very high levels of cholesterol and triglycerides in blood, and unusual and very severe xanthomas. He had no evidence of neurocognitive or retinal defects.

Medical Research: What was most surprising about the results?

Dr. Malloy: Apolipoprotein E is an integral brain protein. A priori, one would expect that its absence would result in some detectable neurocognitive defect yet we found none.

We had previously shown that apolipoprotein E is also found in the retina, but our patient had no deleterious effect on his visual function from it’s absence.

Medical Research: What should clinicians and patients take away from your report?

Dr. Malloy: Minimizing apolipoprotein E4 levels in brain tissue may provide a wholly new venue for intervention in Alzheimer disease and other neurodegenerative disorders. Our observations suggest that proposed strategies for apolipoprotein E knockdown that are brain specific may now be entertained seriously.

Citation:

Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function
 Angel C. Y. Mak, PhD; Clive R. Pullinger, PhD; Ling Fung Tang, PhD; Jinny S. Wong, BS; Rahul C. Deo, MD, PhD; Jean-Marc Schwarz, PhD; Alejandro Gugliucci, MD, PhD; Irina Movsesyan, BS; Brian Y. Ishida, PhD; Catherine Chu, BS; Annie Poon, BS; Phillip Kim, MD; Eveline O. Stock, MD; Ernst J. Schaefer, MD; Bela F. Asztalos, PhD; Joseph M. Castellano, PhD; Tony Wyss-Coray, PhD; Jacque L. Duncan, MD; Bruce L. Miller, MD; John P. Kane, MD, PhD; Pui-Yan Kwok, MD, PhD; Mary J. Malloy, MD

Last Updated on October 18, 2014 by Marie Benz MD FAAD