Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice

What is it about?

Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer’s disease (AD) whereas apolipoprotein E3 (ApoE3) is neutral ApoE allelic variant. The most important non-genetik risk factor of AD is aging. We explored whether cholinergic dysfunction, which increases during aging and is a hallmark of AD, is accentuated by human apoE4 using transgenic targeted replacement mice. We found that presynaptic cholinergic marker vesicular acetylcholine transporter in the hippocampus and the corresponding electrically evoked release of acetylcholine, are both similar in 4-month-old apoE4 and apoE3 mice. Both parameters decreased with age but the decrease was significantly more pronounced in 12-month-old ApoE4 than ApoE3 mice. In addition, the relative representation of the M1 receptor subtype that plays an important role in cognition and memory decreased during aging in apoE4 mice.

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Why is it important?

These findings points to the importance of ApoE phenotype in age-related decline of cholinergic transmission in hippocampus and likely in pathogenesis of Alzheimer’s disease.