Apolipoprotein E ε4 is associated with neuronal loss in the substantia nigra in Alzheimer's disease

Apolipoprotein E ε4 (ApoE ε4) is associated with an earlier age at onset of Alzheimer's (AD) and possibly Parkinson's disease, suggesting a general role for ApoE ε4 in neuronal plasticity. Among 31 prospectively assessed subjects with pathologically confirmed AD (without Lewy bodies), ε4+ subjects had a longer duration of disease (by 2.8 years, p = 0.04). Only cell loss in the substantia nigra (p = 0.002) was associated with ε4. Neither neurofibrillary tangles nor plaque counts were associated with ε4. Cell counts of pigmented neurons in single midbrain sections in ε4+ specimens were 72% of those in ε4-substantia nigra (p = 0.04). These findings confirm that cell loss in the substantia nigra is associated with ε4 in AD.