Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants

Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE epsilon 4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE epsilon 4. Our results show that the presence of APOE epsilon 4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE epsilon 4 have higher CSF NFL levels than non-epsilon 4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of epsilon 4. (C) 2011 Published by Elsevier Inc.