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In Reply We believe that our findings1 do not negate the evidence that apolipoprotein E (apoE) 4 plays an active role in the development of neurocognitive disorders because abundant evidence supports deleterious activity of the E4 isoform. The observation that there is essentially no neurocognitive deficit in our middle-aged patient who was unable to produce any apoE supports the belief that this protein does not have an essential role in the development or later function of the brain, while suggesting that there may be a surrogate protein subserving its roles, including the cerebral transport of cholesterol. Discovery of 1 or more surrogates would enhance knowledge of lipid transport in the brain.
Malloy MJ, Kane JP. Congenital Absence of Apolipoprotein E and Neurological Function—Reply. JAMA Neurol. 2014;71(12):1579. doi:10.1001/jamaneurol.2014.3345