Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease

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Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease

Postby BrianR » Mon Feb 11, 2019 4:51 pm

After listening to the Peter Attia interview with Francisco Gonzalez-Lima yesterday, I thought this was relevant.

The paywalled article is:
Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models
https://www.nature.com/articles/s41593-018-0329-4
https://doi.org/10.1038/s41593-018-0329-4


You can also read the freely available Science Daily summary: New Alzheimer's therapy with brain blood flow discovery?

Interesting extract from the Discussion
Capillary obstruction due to tissue inflammation has been observed in a variety of organ systems (typically at higher incidence than observed here), and has been shown to contribute to the development of pathology and disease33–39. Inflammation is a persistent and well-recognized feature of Alzheimer’s disease, and previous work has demonstrated an increase in inflammatory adhesion receptors on endothelial cells40–42, which probably underlies the capillary stalling we observed. A major contributor to this inflammation is increased reactive oxygen species induced by brain exposure to Aβ oligomeric aggregates26. These reactive oxygen species cause a loss of cerebrovascular flow regulation and probably drive the expression of leukocyte-binding receptors on the endothelial cell surface, such as ICAM1 and VCAM1. Our observation that certain capillary segments were more likely to stall suggests that the underlying vascular inflammation may not be uniform.

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Re: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s dise

Postby aphorist » Mon Feb 11, 2019 6:31 pm

Interesting. I played w/ methylene blue a bit after that podcast. It's very annoying that it stains everything. I need to find a pill form, if you know any.

Another consideration is Ginkgo or maybe low dose Telmisartan.

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Re: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s dise

Postby StevenL » Thu Feb 14, 2019 1:25 pm

I thought this interview was VERY enlightening. I got more out of it than the other ones I've checked out. And his theories do not conflict with what Bredeson is saying about multiple pathways to AD. If in the end it's a blood flow problem in a certain areas of the brain, anything that effects that will be a pathway; Metabolic issues/CVD (vascular side)/infectious damage/trauma and anything else.

Edit: To be more specific, as Attia summarizes, "Gonzalez-Lima explains "the vascular hypothesis of Alzheimer’s disease which says the central problem is a progressive neuronal energy crisis of impaired blood flow to the brain and impaired mitochondrial respiration."

Thus anything that:
stops slows or reverses impairment of blood flow and/or
facilitates adequate mitochondrial respiration
Is of interest for prevention and treatment of AD.

And the Methylene Blue info is golden!

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Re: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s dise

Postby Larsmars11 » Thu Feb 21, 2019 6:38 am

EVERYONE should read the "Science Daily" summary on this, because the top scientist on the study at Cornell says, " this could be a big game-changer for AD patients" and they have already identified 20 drugs which may alleviate the problem, many of which r already FDA approved, so big help seemingly could arrive pretty quickly. I would also note the Bredesen book says zero about the vascular hypothesis (different from vascular dementia), so Bredesen has some serious explaining to do in his next book, in my opinion. if the vascular hypothesis is very important, it would seem to mean that some of what Bredesen theorizes is of minor importance, maybe even wrong.

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Re: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s dise

Postby Larsmars11 » Thu Feb 21, 2019 7:39 am

the reason the Cornell Prof. Shaffer says this could be "a complete game-changer for AD suffers" is that they know how to get an improved blood flow, and this flow leads to "an IMMEDIATE restoration of cognitive performance of spatial and memory-forming tasks". I don't know a lot, but it sounds huge to me. wonder if this is any mention of plaques and tangles, or trophic shortages, or toxins, or genetics. a some point don't these parallel tracks need to converge and cohere and prioritize the factors ?

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Re: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s dise

Postby mike » Thu Feb 21, 2019 9:27 am

Bredesen does talk about nutritional AD, where not enough nutrients are getting to the brain, which is why he suggests a keto diet. Cerebral blood flow would be another of those factors affecting this side. But this is not all - the blood vessels act as the nutrient supply line, but also the waste system. Without proper flow, you get less clearing of AB plaque and other nasties the cells want to get rid of.
Sonoma Mike
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Re: Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s dise

Postby StevenL » Fri Mar 01, 2019 11:18 am

Everyone should definitely listen to this Peter Attia interview with Francisco Gonzalez-Lima.

Gonzalez-Lima has strong opinions about AB plaque etc as a focus for AD. He thinks researchers have been fixatedly working on the wrong thing and this is why no progress has come.


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