APOE and early-onset autosomal dominant Alzheimer disease: Conversely, testosterone, which has similar anti-inflammatory properties, has also been shown to interact with APOE ɛ4 to impact cognitive function and Alzheimer’s disease risk.59–61 Animal studies showed that APOE ɛ4 can reduce androgen receptor levels in the brain, suggesting that APOE ɛ4 carriers may be particularly vulnerable to the effects of lower testosterone.61 Sundermann et al.62 found that the association between lower testosterone and higher levels of cerebrospinal fluid phosphorylated tau were strongest among female APOE ɛ4 carriers.