Naylor JC, Kilts JD, Hulette CM, Steffens DC, Blazer DG, Ervin JF, Strauss JL, Allen TB, Massing MW, Payne VM, Youssef NA, Shampine LJ, Marx CE.
Allopregnanolone levels are reduced in temporal cortex in patients with Alzheimer's disease compared to cognitively intact control subjects.
Biochim Biophys Acta. 2010 Aug;1801(8):951-9.
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This report from Naylor and colleagues provides human data that support our basic science findings that allopregnanolone level was decreased in the 3xTgAD mouse model. Our findings in the 3xTgAD mouse indicated that at a young/pre-AD pathology stage (three months of age), allopregnanolone was significantly lower in the male 3xTgAD mouse cortex relative to age-matched non-Tg mice. Further, allopregnanolone reversed the neurogenic and learning and memory deficits in these mice.
Naylor et al. find that allopregnanolone was further decreased in the end-life temporal cortex of AD patients with an Apo4 allele. Collectively, the basic and clinical data suggest that a decline in allopregnanolone could be an early event in the pathogenesis of the disease and a potential therapeutic intervention.
Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, Thompson RF, Brinton RD.
Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease.
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6498-503.