New paper suggests that ketosis may be helpful for ApoE4 carriers

[Julie G]

A new paper finds that ketosis may be especially helpful for ApoE4 carriers.

Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention.

https://www.ncbi.nlm.nih.gov/pubmed/29967007

SIGNIFICANCE STATEMENT
We uncovered hexokinase as a key cytosolic point in the glucose metabolism that is differentially modulated by the three ApoE genotypes. The differences in hexokinase expression and activity exhibited in the three ApoE brains may underlie their distinct impact on brain glucose utilization and further susceptibility to AD. Therefore, a therapeutic approach that could circumvent the deficiencies in the cytosolic metabolism of glucose by providing glucose metabolizing intermediates, e.g., pyruvate, may hold benefits for ApoE4 carriers, who are at high risk for AD. The bioenergetic robustness may translate into enhanced synaptic activity and, ultimately, reduces the risk of developing AD and/or delays the onset of clinical manifestation.

[Fiver]

Reading....

I found this interesting.....I want to know more about how other non-glucose substrates could be fed into glycolysis or later, directly into the TCA cycle to bypass the upstream blockages.

"Therefore, a therapeutic approach that could circumvent the deficiencies in the cytosolic metabolism of glucose by providing glucose metabolizing intermediates, e.g., pyruvate, may hold benefits for ApoE4 carriers, who are at high risk for AD. The bioenergetic robustness may translate into enhanced synaptic activity and, ultimately, reduces the risk of developing AD and/or delays the onset of clinical manifestation."

If that's all that is required....well that certainly seems possible....

[SusanJ]

It's a mouse study, but I can't help but wonder what this comment on ketone body utilization might mean for a 3/4 human (like me!)

Interestingly, on the uptake and metabolism of ketone bodies, the secondary energy source for the brain, ApoE2 and ApoE4 brains showed a similar level of robustness, whereas ApoE3 brains presented a relatively deficient profile.

[circular]

Very cool. Look forward to reading and seeing this play out!

[TWBD]

SusanJ, I feel like a kindergartner when it comes to understanding research (and feeling rather ‘deficiency unrobust’ at the moment. I was wondering as a fellow 3/4’r if that put me in the category of an ApoE3 or 4 brain?

[slacker]

SusanJ, I feel like a kindergartner when it comes to understanding research (and feeling rather ‘deficiency unrobust’ at the moment. I was wondering as a fellow 3/4’r if that put me in the category of an ApoE3 or 4 brain?

maybe not E3 or E4 dependent, but level of education (kindergartner). Understanding will improve as you move through elementary school, middle school, etc! Although this article may need a STEM bachelor's degree at least

Don't sweat it. This is definitely geek level, which is wonderful for the geeks, but not necessary for mere mortals. A lot of research shine a light on possibilities, but doesn't necessarily present us with hard data on what to do for cognitive health right now.

[Searcher]

The abstract states:

"PGC-1α overexpression ameliorated ApoE4-induced deficits in glycolysis and mitochondrial respiration."

This is useful to know, because PGC-1α expression can be influenced by what we do.

Cold exposure, fasting and exercise all tend to increase PGC-1α expression. They may be simple ways of slowing the cognitive decline associated with deficient glucose metabolism.

[Fiver]

Nicely distilled summary Searcher!!!

[Searcher]

Fiver,

Just tying this abstract in with existing knowledge to draw practical implications.

More background info here:

https://www.physiology.org/doi/10.1152/advan.00052.2006

[Fiver]

....that's a really important skill to have!