Leptin, Low Carb, and Alzheimer's

Abstract 

Accumulation of amyloid-β (Aβ) is a key event mediating the cognitive deficits in Alzheimer's disease (AD) as Aβ promotes synaptic dysfunction and triggers neuronal death. Recent evidence has linked the hormone leptin to AD as leptin levels are markedly attenuated in AD patients. Leptin is also a potential cognitive enhancer as it facilitates the cellular events underlying hippocampal learning and memory. Here we show that leptin prevents the detrimental effects of Aβ_1–42 on hippocampal long-term potentiation. Moreover leptin inhibits Aβ_1–42-driven facilitation of long-term depression and internalization of the 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid (AMPA) receptor subunit, GluR1, via activation of PI3-kinase. Leptin also protects cortical neurons from Aβ_1–42-induced cell death by a signal transducer and activator of transcription-3 (STAT-3)-dependent mechanism. Furthermore, leptin inhibits Aβ_1–42-mediated upregulation of endophilin I and phosphorylated tau in vitro, whereas cortical levels of endophilin I and phosphorylated tau are enhanced in leptin-insensitive Zucker fa/fa rats. Thus leptin benefits the functional characteristics and viability of neurons that degenerate in AD. These novel findings establish that the leptin system is an important therapeutic target in neurodegenerative conditions.

http://www.neurobiologyofaging.org/article/S0197-4580(12)00425-3/abstract

I doubt the author's conclusion will lead anywhere.  It is well established that high levels of triglycerides  prevent leptin from crossing the blood brain barrier.  My conjecture - and admittedly this is way over my head but a plausible conjecture none the less - is that this is one of the ways that high carb diets negatively impact development of "AD".
First, high carb diets drive high triglyceride levels, and with subsequent development of insulin resistance, high insulin levels.  The high trigs mean that less leptin will interact in the brain, perhaps creating the effects described above which drive amyloid-B accumulation at faster rates.
High insulin levels means that the body's scavenger system for amyloid-B, insulin degrading enzyme, is busy with insulin and never has time to attend to amyloid-B.
Third, fasting results in the body finding and using as much protein in the body as possible, and there's some evidence that this "protein scavenging" reduces build of of AGEs (a protein damaged by glycation) and other "junk" proteins that wind up in the plaques associated with AD.
Lastly, high blood sugar levels drives higher levels of advanced glycation end products, which are also accelerants in the plaques that characterize AD.

The example of the diabetics is telling - they get AD at higher rates than everyone else.  It would be interesting to know - can AD develop in a person who maintains normal to low blood glucose across their entire lifespan?  Or, the same question stated differently:  has a person ever been diagnosed with AD who maintained optimal blood sugar levels across a lifetime (or most of a lifetime)?