Mitochondrial Dysfunction in E4 carriers

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
User avatar
Julie G
Mod
Mod
Posts: 9187
Joined: Sat Oct 26, 2013 6:36 pm

Re: Mitochondrial Dysfunction in E4 carriers

Post by Julie G »

This looks like a potentially helpful paper for our population. I'd love to see full-text :D
Mitochondrial Dysfunction: Cause and Consequence of Alzheimer's Disease
http://www.sciencedirect.com/science/ar ... via%3Dihub
Abstract
The etiology of common, nonfamiliar late-onset Alzheimer's disease (LOAD) is only partly understood and seems to be extremely complex including many genetic and environmental factors. The most important environmental risk factor to develop LOAD is aging itself. Aging and LOAD are considered to be strongly linked to mitochondrial dysfunction and enhanced oxidative stress. In this review, we focus on the interaction between mitochondrial dysfunction in aging especially on defects of the respiratory chain of the oxidative phosphorylation system resulting in enhanced oxidative stress and the interplay between aging-associated mitochondrial defects and LOAD-associated mitochondrial failure. The deleterious effects of the two hallmarks of LOAD, amyloid beta, and hyperphosphorylated tau, on mitochondrial function, movement, and morphology are described as well as the toxic effects of the most relevant genetic risk factor of LOAD, the apolipoprotein E4 allele. Finally, the review provides an overview about drugs and nutritional ingredients which improve mitochondrial function or/and act as antioxidants and discusses their potential role in the treatment of LOAD.
circular
Senior Contributor
Senior Contributor
Posts: 5565
Joined: Sun Nov 03, 2013 10:43 am

Re: Mitochondrial Dysfunction in E4 carriers

Post by circular »

Wow that looks good. I'm trying to sort out whether AD has its own unique mitochondrial dysfunction or whether it exacerbates the mitochondrial function that's part of aging (or both), while E4 is its own driver on top of many standard developed world inputs.


Sent from my iPhone using Tapatalk
ApoE 3/4 > Thanks in advance for any responses made to my posts.
User avatar
Stavia
Contributor
Contributor
Posts: 5255
Joined: Tue Apr 29, 2014 6:47 pm
Location: Middle Earth

Re: Mitochondrial Dysfunction in E4 carriers

Post by Stavia »

Juliegee wrote:This looks like a potentially helpful paper for our population. I'd love to see full-text :D
Mitochondrial Dysfunction: Cause and Consequence of Alzheimer's Disease
http://www.sciencedirect.com/science/ar ... via%3Dihub
Abstract
The etiology of common, nonfamiliar late-onset Alzheimer's disease (LOAD) is only partly understood and seems to be extremely complex including many genetic and environmental factors. The most important environmental risk factor to develop LOAD is aging itself. Aging and LOAD are considered to be strongly linked to mitochondrial dysfunction and enhanced oxidative stress. In this review, we focus on the interaction between mitochondrial dysfunction in aging especially on defects of the respiratory chain of the oxidative phosphorylation system resulting in enhanced oxidative stress and the interplay between aging-associated mitochondrial defects and LOAD-associated mitochondrial failure. The deleterious effects of the two hallmarks of LOAD, amyloid beta, and hyperphosphorylated tau, on mitochondrial function, movement, and morphology are described as well as the toxic effects of the most relevant genetic risk factor of LOAD, the apolipoprotein E4 allele. Finally, the review provides an overview about drugs and nutritional ingredients which improve mitochondrial function or/and act as antioxidants and discusses their potential role in the treatment of LOAD.

here you go
mito.pdf
Moderator note - I deleted the attached paper (doi:10.1016/B978-0-12-394625-6.00007-6) because our copyright infringement policy prohibits it. Members in jurisdictions for which access to Sci-Hub is legal may want to search for the paper there.
LA18
Senior Contributor
Senior Contributor
Posts: 118
Joined: Thu May 29, 2014 10:13 pm

Re: Mitochondrial Dysfunction in E4 carriers

Post by LA18 »

Thanks for posting this and the review article (and to Julie for finding). I was so anxious to read this one that I considered purchasing it yesterday. Glad I waited!
User avatar
Stavia
Contributor
Contributor
Posts: 5255
Joined: Tue Apr 29, 2014 6:47 pm
Location: Middle Earth

Re: Mitochondrial Dysfunction in E4 carriers

Post by Stavia »

LAC1965 wrote:Thanks for posting this and the review article (and to Julie for finding). I was so anxious to read this one that I considered purchasing it yesterday. Glad I waited!
LAC1965 don't ever buy anything this year, its a waste of money. I just live in a completely different part of the world from you guys so when you are up I am asleep so there will always be a lag. And I work full-time so I have to find a gap to get the paper. Lastly I dunno how to upload from my ipad so if I am not near a desktop it may be a day or so.
I will be able to do this until the end of the year. I will let the forum know if I can continue accessing full text next year.
User avatar
Russ
Senior Contributor
Senior Contributor
Posts: 566
Joined: Fri Feb 07, 2014 10:33 am

Re: Mitochondrial Dysfunction in E4 carriers

Post by Russ »

Just bringing back the link to this prior post...
https://www.apoe4.info/forums/viewtopic ... ria#p10281

...referencing this paper...
http://www.impactaging.com/papers/v6/n4 ... 00654.html

...on how CR and fasting can be a tool to strengthen mitochondria.
In short they looked at the mitochondria form in young old and LLI's [Long-Lived Individuals] and found that the LLI's had noticeably aggregated (hyperprofused) mitochondria and propose that this is an energy efficiency thing naturally occurring in some LLI old people but phenomenologically similar to conditions observed in calorie restricted people.
Russ
E3/4
Eat whole, real, flavorful food - fresh and in season... and mix it up once in a while.
User avatar
Julie G
Mod
Mod
Posts: 9187
Joined: Sat Oct 26, 2013 6:36 pm

Re: Mitochondrial Dysfunction in E4 carriers

Post by Julie G »

Given that many different sources, including the computational engineering result in this thread: viewtopic.php?f=16&t=1671, are pointing to mitochondrial deficiency as our primary driver of pathology, I thought I'd resurrect this old thread.

What are you doing to support your mitochondria? I suspect there's a lot more that I should know...
circular
Senior Contributor
Senior Contributor
Posts: 5565
Joined: Sun Nov 03, 2013 10:43 am

Mitochondrial Dysfunction in E4 carriers

Post by circular »

Acetyl-L-Carnitine
CoQ10

At least I think these support mitos, but don't ask me for details! About 4-6 months ago I just felt like I *must* have mitochondrial stress given all I've had going on, and that I better do something and later I'll figure out if it's right! Bad protocol but there it is. Some things I do after following reasonable procedures, others not, but I have figured I'll look into it within a year, too short term to cause much damage I hope!
ApoE 3/4 > Thanks in advance for any responses made to my posts.
User avatar
Julie G
Mod
Mod
Posts: 9187
Joined: Sat Oct 26, 2013 6:36 pm

Re: Mitochondrial Dysfunction in E4 carriers

Post by Julie G »

Thanks, Circ. I take versions of those two as well. I'd read that ubiquinol may be more bio-available than CoQ10, but who knows? I'm particularly curious about PQQ (pyrroloquinoline quinone.) Anyone taking that? I'd appreciate any feedback.

I've been poking into ways to improve mitochondrial health. As you’ll recall, Russ recently posted this link about the work of Dr. Allen Roses whose work has largely focused on the mitochondrial implications of E4s inability in the brain to metabolize energy sources:
Do we all have Alzheimer’s completely wrong? This may says yes
http://www.pri.org/stories/2015-04-30/d ... n-says-yes

Dr. Roses is considered a maverick in the Alzheimer’s by bucking the amyloid cult, but he’s still mainstream enough to believe that pharmaceuticals hold the answer. I’ve been looking into his solution to our energy shortage. It involved a drug called pioglitazone. Rodent and human studies have already shown that low-dose pioglitazone improved mitochondrial function and enabled them to better metabolize energy sources.
"At a point in time when people are about to suffer from mitochondrial inadequacy in their brain, the aim of the study [with Takeda] is to double the number of mitochondria and increase their ability to metabolize glucose and oxygen," Roses says.
It looks like the drug is currently available and being used to treat T2D:
https://en.m.wikipedia.org/wiki/Pioglitazone

Here's a paper describing it's mechanism of action:
http://www.ncbi.nlm.nih.gov/pubmed/11594239
Thiazolidinediones, such as pioglitazone, are synthetic ligands for peroxisome proliferator-activated receptors (PPARs). They alter the transcription of genes influencing carbohydrate and lipid metabolism, resulting in changed amounts of protein synthesis and, therefore, metabolic changes. Pioglitazone improves glycaemic control in people with Type 2 diabetes by improving insulin sensitivity through its action at PPAR gamma 1 and PPAR gamma 2, and affects lipid metabolism through action at PPAR alpha. The results of these interactions include increases in glucose transporters 1 and 4, lowered free fatty acids, enhanced insulin signalling, reduced tumour necrosis factor alpha (TNF alpha) and remodelling of adipose tissue. Together, these can increase glucose uptake and utilisation in the peripheral organs and decrease gluconeogenesis in the liver, thereby reducing insulin resistance.
Here's a good summary of the pioglitazone research as it relates to Alzheimer's:
http://www.alzforum.org/therapeutics/pioglitazone
circular
Senior Contributor
Senior Contributor
Posts: 5565
Joined: Sun Nov 03, 2013 10:43 am

Re: Mitochondrial Dysfunction in E4 carriers

Post by circular »

That article is a great summary of that amyloid/mito bifurcation. I also suspect more and more that there are going to be additional contributing causes, especially from the immune department. I can imagine if not articulate there could be a cascade that begins with the immune system and ends with Alzheimer's, as opposed to the immune system just becoming an issue in the brain. I think it's doing us a disservice to presume there can only be one type of physiological cascade that leads to Alzheimer's presentations, whether it's amyloid or mito or … It seems to me the brain receives data and biochemical feedback from all over the body and cells such that multiple pathways could lead to AD?

This issue of mavericks in medicine is rather fascinating! Someone could do a documentary on the various mindsets/philosophy and approaches to medical science and clinical practice. I'm beginning to think that evidence-based medicine is just as half-baked as that which isn't!
ApoE 3/4 > Thanks in advance for any responses made to my posts.
Post Reply