Pure Pedantry found this paper on leptin’s effects in the hippocampus, and then went on to wonder
I have never heard of a link between leptin and memory. They also make this link between ABeta mice and leptin. ABeta is a protein whose accumulation has been linked to Alzheimer’s. Mice that create to much ABeta show cognitive deficits. They show that an ABeta overproducing mouse also showed improvement when treated with leptin — and link that result to the observation that leptin decreases ABeta. I am not sure what to make of that, but there is probably a metabolic story related to ABeta production.
Since he is lucky enough to have a fellow Seed blogger who currently works with AD transgenic mice, I wanted to expand on his thoughts a bit.
Leptin can mitigate increases in brain amyloid load a couple of ways. Firstly, it can decrease the amount of amyloid produced by reducing the activity of an enzyme called beta-secretase, which cleaves amyloid free from its precursor protein. Secondly, leptin can modulate the uptake of Abeta protein by apoE and thus reduce extracellular levels of the protein. Which is especially good because Abeta is thought to form fibrils that muck up synapses when just floating around in the brain (the formation of plaques may in fact be the result of a clearance mechanism). Leptin might also enhance cognition generally by altering the composition of lipid rafts in a manner conducive to molecular trafficking and synaptic transmission.
The paper PP cited was interesting because it clearly showed a bimodal relationship between leptin and cognitive performance. Going back to the amyloid/Alzheimer’s Disease (AD) story, the preliminary evidence suggests that leptin may be a potential therapeutic for the treatment of AD, but I have to speculate that the dose response curve may shift a bit– what is acceptable for a “successfully aging” individual may actually have deletorious consequences for AD patients if they are already compromised. Plus, leptin has been implicated in various inflammatory processes so there is the possibility that disease progression may actually be enhanced.
Nice find, PP!