5 ms·

I am not sure I buy into the author's calcineurin/mitochondria hypothesis. There is a much more direct causal link as auto-immunity has been implicated in AD p

I am not sure I buy into the author's calcineurin/mitochondria hypothesis. There is a much more direct causal link as auto-immunity has been implicated in AD progression for years, e.g. [1-11]. I can't find the paper right now, but I once saw a very compelling longitudinal study where they regularly measured cognitive performance as well as several immunity markers in older subjects. Basically, every transient increase in antibody levels (IIRC, but they may have been tracking some other marker of immune system activation) was followed by a step decline in cognitive performance. [1] Lopez (1991) Serum auto-antibodies in Alzheimer's disease [2] Aisen (1996) Inflammation and Alzheimer disease [3] D'Andrea (2005) Add Alzheimer’s disease to the list of autoimmune diseases [4] Carter (2010) Alzheimer's Disease: A Pathogenetic Autoimmune Disorder Caused by Herpes Simplex in a Gene-Dependent Manner [5] Reddi et al (2011) Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Aβ and RAGE peptides [6] Sardi et al (2011) Alzheimer's disease, autoimmunity and inflammation. The good, the bad and the ugly [7] Marchese (2013) Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease [8] Li et al. (2018) Dementia and Alzheimer's disease risks in patients with autoimmune disorders [9] Arshavski (2020) Alzheimer’s Disease: From Amyloid to Autoimmune Hypothesis [10] Itzhaki et al (2020) Do infections have a role in the pathogenesis of Alzheimer disease? [11] Lim et al (2020) Alzheimer Disease Pathogenesis: The Role of Autoimmunity

renewiltord 5y ago
Sorry, haven’t read these yet, but any antibodies? Like any immune response makes you duller and at greater risk? Eek.
- burning_hamster 5y ago
  Like I said, I can't find the study right now, and I originally saw the data anywhere between 5-10 years ago. They may also have been measuring some cytokine. Even without AD, memories really aren't reliable over that time span. The point the authors were trying to make is that if you have AD, any inflammation, even asymptomatic ones, will potentially worsen your cognitive performance. The most interesting feature of that graph was to me that the cognitive performance actually remained fairly constant in between infections/inflammations, and decline was not gradual but in a step-wise fashion.
  - axutio 5y ago
    Also interesting is ISRIB [0,1], which is intended to negate the cognitive impacts of stress memory accumulated over years of immune response, and possibly as a result of TBI as well [2]. [0] https://en.wikipedia.org/wiki/ISRIB https://en.wikipedia.org/wiki/ISRIB [1] https://doi.org/10.1073/pnas.1815767116 https://doi.org/10.1073/pnas.1815767116 [2] https://doi.org/10.1073/pnas.1707661114 https://doi.org/10.1073/pnas.1707661114
noyeastguy 5y ago
I absolutely agree with this. My great grandmother had Alzheimers as well as Hidradenitis suppurativa, which I have inherited from her. I switched to a yeast and wheat free diet many years ago to relieve symptoms of HS. Not only did it resolve my HS, but also migraines and many other inflammatory issues. Looks like there is research around Alzheimer's and Dectin-1 signaling which is involved in innate immunity to fungi, including bread yeast (Saccharomyces cerevisiae). It's absolutely insane to me that people eat a pathogen that triggers an innate immune response. A inflammation response to yeast is coded into our cells, if it weren't we'd be killed by unbaked bread. Why then do most processed foods contain it? We're taxing and confusing our immune systems by eating it.
- micro_cam 5y ago
  This isn’t a well understood area at all but the idea that yeast / fermented food consumption helps us regulate our immune system in a good way has also been studied.
  - noyeastguy 5y ago
    Yep, it's kind of a double-edged sword. On one hand an over-active immune response can be great for fighting cancers and opportunistic infections possibly. But too much inflammation will wear down our bodies and trigger auto-immune responses.
- klipt 5y ago
  Is there less Alzheimer's in cultures that don't eat bread (e.g. where rice or potatoes are a staple instead)? Maybe in bread heavy cultures it's not a widespread issue because the majority of people have evolved some kind of resistance?
  - ejolto 5y ago
    You tend to get Alzheimer's after you are done having children, so resistance wouldn't evolve.
deleted 5y ago
[deleted]

renewiltord 5y ago

Sorry, haven’t read these yet, but any antibodies? Like any immune response makes you duller and at greater risk? Eek.

burning_hamster 5y ago
Like I said, I can't find the study right now, and I originally saw the data anywhere between 5-10 years ago. They may also have been measuring some cytokine. Even without AD, memories really aren't reliable over that time span. The point the authors were trying to make is that if you have AD, any inflammation, even asymptomatic ones, will potentially worsen your cognitive performance. The most interesting feature of that graph was to me that the cognitive performance actually remained fairly constant in between infections/inflammations, and decline was not gradual but in a step-wise fashion.
- axutio 5y ago
  Also interesting is ISRIB [0,1], which is intended to negate the cognitive impacts of stress memory accumulated over years of immune response, and possibly as a result of TBI as well [2]. [0] https://en.wikipedia.org/wiki/ISRIB https://en.wikipedia.org/wiki/ISRIB [1] https://doi.org/10.1073/pnas.1815767116 https://doi.org/10.1073/pnas.1815767116 [2] https://doi.org/10.1073/pnas.1707661114 https://doi.org/10.1073/pnas.1707661114

noyeastguy 5y ago

I absolutely agree with this. My great grandmother had Alzheimers as well as Hidradenitis suppurativa, which I have inherited from her. I switched to a yeast and wheat free diet many years ago to relieve symptoms of HS. Not only did it resolve my HS, but also migraines and many other inflammatory issues. Looks like there is research around Alzheimer's and Dectin-1 signaling which is involved in innate immunity to fungi, including bread yeast (Saccharomyces cerevisiae). It's absolutely insane to me that people eat a pathogen that triggers an innate immune response. A inflammation response to yeast is coded into our cells, if it weren't we'd be killed by unbaked bread. Why then do most processed foods contain it? We're taxing and confusing our immune systems by eating it.

micro_cam 5y ago
This isn’t a well understood area at all but the idea that yeast / fermented food consumption helps us regulate our immune system in a good way has also been studied.
- noyeastguy 5y ago
  Yep, it's kind of a double-edged sword. On one hand an over-active immune response can be great for fighting cancers and opportunistic infections possibly. But too much inflammation will wear down our bodies and trigger auto-immune responses.
klipt 5y ago
Is there less Alzheimer's in cultures that don't eat bread (e.g. where rice or potatoes are a staple instead)? Maybe in bread heavy cultures it's not a widespread issue because the majority of people have evolved some kind of resistance?
- ejolto 5y ago
  You tend to get Alzheimer's after you are done having children, so resistance wouldn't evolve.

deleted 5y ago

[deleted]