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Genetic differences & Alzheimer's disease

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
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Genetic differences & Alzheimer's disease

Postby Searcher » Thu Feb 15, 2018 7:29 am

An example:

http://europepmc.org/abstract/MED/24755620

Sub-networks (SNs) involved in glutamate signaling were significantly overrepresented in Alzheimer's.

This is just one example. A list of genome-wide association studies can be found here:

http://www.ebi.ac.uk/gwas/search?query=Alzheimer

Two homozygous APOE4 carriers might show different outcomes, in terms of eventual AD, even when they adopt identical practices. Therefore studies with small numbers are not reliable predictors of eventual outcomes in a given individual.

Large-scale trials are more likely to be applicable to a given individual, since SNPs and networks of SNPs are more likely to be randomly distributed in larger populations.

What does this mean for daily life?

Rely more on large-scale studies and genome-wide associations, less on anecdotal evidence or small-scale studies.

Rely more on studies of health outcomes (disability or mortality) than studies of biomarkers, because the biomarkers used are only a subset of the relevant biomarkers and interactions (known and unknown).

Keep making a good day and a good week, because your efforts will be rewarded more surely than if you worry obsessively about life in future decades. Besides, excessive worry increases cortisol levels. Expand your horizons to include all that makes health worth having and life worth living.

Of course, as genome-wide analysis becomes more commonplace, we'll have increasingly better information about what interventions will work best for each individual. The future seems rosier because of our constantly expanding knowledge.

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Re: Genetic differences & Alzheimer's disease

Postby NF52 » Thu Feb 15, 2018 12:19 pm

Searcher wrote:Two homozygous APOE4 carriers might show different outcomes, in terms of eventual AD, even when they adopt identical practices.
What does this mean for daily life?
Rely more on large-scale studies and genome-wide associations, less on anecdotal evidence or small-scale studies.
Rely more on studies of health outcomes (disability or mortality) than studies of biomarkers, because the biomarkers used are only a subset of the relevant biomarkers and interactions (known and unknown).
Keep making a good day and a good week, because your efforts will be rewarded more surely than if you worry obsessively about life in future decades. Besides, excessive worry increases cortisol levels. Expand your horizons to include all that makes health worth having and life worth living.


Words of wisdom, Searcher, especially about the rewards of not worrying too much about future decades. I am hopeful, however, that as meta-analyses of biomarkers become more sophisticated, we will know what is a helpful breeze and what is an incoming tornado and be able to make decisions accordingly.
4/4 and still an optimist!

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Re: Genetic differences & Alzheimer's disease

Postby ZenGinner » Thu Feb 15, 2018 8:11 pm

Love this. Thanks!


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Re: Genetic differences & Alzheimer's disease

Postby circular » Fri Feb 16, 2018 7:07 am

Searcher wrote:Expand your horizons to include all that makes health worth having and life worth living.

Love this Searcher! Keep guiding us in your valuable statistical perspectives. Being rather zenish myself, I view the world as replete with paradox, thus, while the statistical perspective needs to be considered and appreciated ...
NF52 wrote:I am hopeful, however, that as meta-analyses of biomarkers become more sophisticated, we will know what is a helpful breeze and what is an incoming tornado and be able to make decisions accordingly.

I have lived in the health tornado and climbed my way out using biomarkers and untested protocols. I have done this without eating a grain-filled Mediterranean diet or intense exercise, which is contraindicated in me. Others are free to call it a placebo affect. I disagree, but I'm the first to say I can't claim to know which aspects of my biomarker-driven protocol have been the most critical, and I firmly believe some probably have been and are useless, and I don't know which ones. I can't say whether I'm being harmed long-term, but I am far healthier and more energetic, a state that has restored my capacity for sustaining more positive outlooks. So I'm willing to keep taking my chances. In fact in addition to not being able to attribute my improvements to the conventional pillars of good health (grain-filled Mediterranean diet and intense exercise), they have come despite 'exponentially' increasing stress as both parents health and cognition fail more and more.

There's no logical way to reconcile n=1 with the statistical worldview, but logic can help clearly articulate the uncertainties inherent in N=1, while N=1 can point to the apparent limitations in the statistical models. Gratefully, to some, there are traditions outside the west that embrace paradox. I would like to hear what a conversation would be like between the statisticians and the 'particles are waves' atomic physicists, but I'd be left in the dust before it began.

This has been a thought exercise brought to you by Circular. Entertain it at your own risk ;)
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Genetic differences & Alzheimer's disease

Postby Julie G » Fri Feb 16, 2018 8:13 am

There's no logical way to reconcile n=1 with the statistical worldview, but logic can help clearly articulate the uncertainties inherent in N=1, while N=1 can point to the apparent limitations in the statistical models. Gratefully, to some, there are traditions outside the west that embrace paradox.

Beautifully said, Circular. To rely on large-scale studies and genome-wide associations preferentially over N=1 is completely illogical. Acknowledging the discrepancies between the two paradigms and diving into the paradoxes is likely where we'll find our answers.

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Re: Genetic differences & Alzheimer's disease

Postby Searcher » Fri Feb 16, 2018 8:48 am

circular wrote:I am far healthier and more energetic, a state that has restored my capacity for sustaining more positive outlooks.


Sounds as if you're winning, Circular!

Probably the most important health outcome is how fully you inhabit and embrace each present moment, whatever it brings.

I've worked with some people who had every advantage in life, but they felt their lives were empty and meaningless (not all of them, of course). I've also worked with some people with the most severe disadvantages imaginable, yet they glowed with acceptance and fulfilment (again, not all of them). As these latter thrived, they seemed to spread courage and joy around them.

To recognize what really matters to you in life, and to live that whole-heartedly, seems the recipe for a great life. No matter what the weather or climate happen to be like.

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Re: Genetic differences & Alzheimer's disease

Postby circular » Fri Feb 16, 2018 8:57 am

I think when looking at the outlooks of those who are at severe disadvantage, one has to also consider what if any supports are in place to help them. Some cultures provide enough support that these challenged people can still 'take to their wings,' while other cultures leave them so bereft of support it's almost impossible for them to find any wings at all.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Genetic differences & Alzheimer's disease

Postby Searcher » Fri Feb 16, 2018 9:10 am

Julie G wrote:To rely on large-scale studies and genome-wide associations preferentially over N=1 is completely illogical. Acknowledging the discrepancies between the two paradigms and diving into the paradoxes is likely where we'll find our answers.


Julie, there are no discrepancies. There is complete agreement because the same paradigm applies.

N=1 reliably informs the person doing the test and very few others (unless they happen to be related to the tester). But such tests can throw up interesting hypotheses that may be proven, in larger trials, to be widely applicable.

Large-scale studies more reliably inform not only the participants, but also many others - because each individual is likely to be nearer to the average of a large population than to one other individual.

For example, a study involving 10,000 women who are APOE4 homozygous carriers is likely to be more applicable to you than a study involving only one such carrier. That's because you're more likely to be like the average of the 10,000 women, genome-wise, than like the one individual woman - unless that individual happens to be related to you.

As genome-wide associations gain usage, smaller and smaller sample sizes will suffice for extrapolations to genomically similar populations.

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Re: Genetic differences & Alzheimer's disease

Postby Julie G » Fri Feb 16, 2018 9:59 am

For example, a study involving 10,000 women who are APOE4 homozygous carriers is likely to be more applicable to you than a study involving only one such carrier. That's because you're more likely to be like the average of the 10,000 women, genome-wise, than like the one individual woman - unless that individual happens to be related to you.

We're in complete agreement.
Rely more on large-scale studies and genome-wide associations, less on anecdotal evidence or small-scale studies.

...with the exception of N=1 as nothing else advises the individual more powerfully.

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Re: Genetic differences & Alzheimer's disease

Postby Searcher » Fri Feb 16, 2018 11:46 am

Julie G wrote:
Rely more on large-scale studies and genome-wide associations, less on anecdotal evidence or small-scale studies.

...with the exception of N=1 as nothing else advises the individual more powerfully.



Julie, N=1 for oneself is tweaking or selecting interventions to fit oneself. Everyone rightly does that. If something disagrees with them, they try changing it a bit or using alternatives. If something is working well, they persist with it. All that makes complete sense.

N=1 by others is less useful to a given individual. Unless the others happen to be identical twins or close relatives who have similar habits and practices to that individual.

So, when large-scale studies show benefits from an intervention (eg., green leafy vegetables improve well-being in many ways), then the unfavorable N=1 outcomes or adverse effects in an individual (eg., too frequent bowel movements) don't overturn the findings of the large-scale study for others.


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