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Letters to the Editor
May 1998

Apolipoprotein Eϵ4 (Epsilon) Allele Does Not Affect the Onset or Symptom Severity in Progressive Supranuclear Palsy

Arch Neurol. 1998;55(5):752-754. doi:

Apolipoprotein E (APOE, gene; apoE, protein) is the major apolipoprotein expressed in the brain,1 and inheritance of the 3 common alleles modifies the risk and age of onset of Alzheimer disease (AD). Apolipoprotein E has also been implicated in cholinergic neuronal survival and synaptogenesis.2-4 The APOE epsilon (ϵ) 4 allele increases the risk and lowers the age of onset of AD and may influence learning in elderly individuals without dementia.2,5 While the APOE genotype influences the risk of onset of late-onset familial and sporadic AD, there are conflicting data regarding the rate of AD progression and severity since both slowing and rapid decline have been suggested.5-11 Patients with progressive supranuclear palsy (PSP), similar to those with AD, exhibit memory dysfunction, widespread degeneration of cholinergic neurons, and neurofibrillary tangles.12-14 However, in contrast to AD, the distribution of APOE allele frequencies in PSP is similar to that of the age-matched controls.15-17 Since basal ganglia and brainstem cholinergic degeneration contributes to PSP motor and behavioral deficits by interrupting 4 of the 5 frontosubcortical pathways mediating these features, we investigated whether the presence of the APOE ϵ4 allele influences age at onset, severity of memory, or overall motor dysfunction in PSP.