Neurofibrillary tangles (NFTs) have been shown in 20% of subacute sclerosing panencephalitis (SSPE) cases. NFTs contain paired helical filaments formed by hyperphosphorylated tau. The intraneuronal tau metabolism and the rate of formation of paired helical filaments can be regulated by interactions between tau and isoforms of Apolipoprotein E (Apo E). Tau binds in vitro to Apo E3, interferes with the hyperphosphorylation of tau and may reduce the formation of NFTs. We investigated cerebrospinal fluid (CSF) Apo E levels in SSPE (n = 37) and age-matched control (n = 38) groups. The median level of total Apo E and Apo E4 were lower in the SSPE than the control group (p < 0.001 and p = 0.002). On the other hand, median Apo E3 level (0.28 +/- 0.23 mu g/ml) was higher in the SSPE group (p < 0.001). Such elevated levels of ApoE3 might play a role in controlling the formation of NFTs in SSPE. Because NFT-associated neurodegeneration is a slow process, comparison of the long-term clinical course of SSPE cases with high and low Apo E3 levels might provide further understanding or the role of these molecules in this disease, and help the planning of neuroprotective treatment. (C) 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.