Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron disease

Background Variants of the apolipoprotein E (APOE) gene influence the age of onset of Alzheimer's disease. APOE may influence the presentation of other neurological diseases. We investigated the relationship between the allelic variants of apolipoprotein E and clinical presentation in motor neuron disease. Methods 123 patients with motor neuron disease and 121 controls were studied. Diagnosis, location of onset and date of onset were recorded prospectively. Genotyping was performed blind to clinical information. Findings Possession of at least one epsilon 4 allele was significantly more common in patients with bulbar onset motor neuron disease (14/33, 42%) than in limb onset patients (20/90, 22%) and controls (26/121, 21%) (chi(2)=4.93, p=0.026 and chi(2)=5.91, p=0.015, respectively). Interpretation These results suggest that the apolipoprotein E epsilon 4 allele may influence the pattern of motor neuron loss in motor neuron disease and that it may affect neuronal function in ways unrelated to the deposition of beta-amyloid or accumulation of neurofibrillary tangles.