title: Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants.
abstract: 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 ε4 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 ε4. Our results show that the presence of APOE ε4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE ε4 have higher CSF NFL levels than non-ε4 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 ε4.
authors: Nathan Kline Institute, Orangeburg, NY 10962, USA. d.bruno@nki.rfmh.org
authors: Davide
authors: D
authors: Bruno
authors: Nunzio
authors: N
authors: Pomara
authors: Jay
authors: J
authors: Nierenberg
authors: James C
authors: JC
authors: Ritchie
authors: Michael W
authors: MW
authors: Lutz
authors: Henrik
authors: H
authors: Zetterberg
authors: Kaj
authors: K
authors: Blennow
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000134:cerebrospinal fluid; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D008568:Memory / Q000502:physiology; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*
chemical_list: D053327:Apolipoprotein E4; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D016900:Neurofilament Proteins; C400783:TOMM40 protein, human; C044882:neurofilament protein L; D006854:Hydrocortisone