Apolipoprotein E and neuromuscular disease - A critical review of the literature

Molecular mechanisms that alter the incidence and rate of neuromuscular dis ease progression are, in many cases, only partially understood. Several rec ent studies have asked whether apolipoprotein E (apoE for the protein, APOE for the gene) influences these aspects of specific neuromuscular disorders , as it does in central nervous system disorders such as Alzheimer disease. Although these studies are open to methodological criticism, several inter esting trends have emerged. First, the APOE4 allele seems to be associated with an increased risk for developing certain neuromuscular diseases, inclu ding diabetic neuropathy and human immunodeficiency viral neuropathy. Secon d, this allele appears to be associated with faster progression of some neu romuscular diseases, including diabetic neuropathy and possibly motor neuro n disease. Third, the APOE2 allele seems to confer protection against devel oping certain neuromuscular diseases, including the amyotrophic lateral scl erosis (ALS)/parkinsonism/dementia complex of Guam. Finally, this allele is associated with a better prognosis in neuromuscular diseases such as motor neuron disease. The effect of various APOE alleles on neuromuscular diseas es therefore parallels their influence on central nervous system diseases.