'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

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circular
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'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by circular »

This may interest some here. I just came across it but haven't had time to read it.

Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology
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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

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Hi circular. Holy cow. That is one long paper. I think I would need all day to really absorb it.

That's a very complex review of the web of networks and approaches for understanding and early detection. There is less about actual treatment options, for now or in the future.

As I read, I found myself growing impatient. Understanding and early detection are important, but then what?

It also made me wonder how accessible the personalized, systems-type medicine will be. Most patients struggle to get their family doctors to do the basics. How will patients access this complex, expensive stuff? It doesn't seem like our current healthcare system can handle personalized medicine for the masses.

Oh my, was that overly critical? Probably just my mood today. :?
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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by circular »

Hi Fiver,

Just based on the little bit of skimming I did, I see this as the hard core side of Dr. Bredesen's POV. Whereas Dr. Bredesen has been criticized for not delineating matters in greater depth and waiting for a more stepwise scientific approach to precision medicine in AD, these authors are showing just what is involved analytically to draw scientifically-sound precision medicine conclusions that will satisfy the strict evidence based camp.

Dr. Bredesen's work is much more lay person friendly, and he among others is saying that despite the need to address all the complexity described in this paper, there is much we can observe, summarize and put to use now using broader strokes.

Not sure if this makes sense. I'm not speaking for anyone, much less Dr. Bredesen; this is my impression, and I'm only referencing Dr. Bredesen for a comparison in how we approach this complicated disease. In my view both are needed, but most of us don't have to master all the complicated issues to improve our health and lower our risk for AD :)
Last edited by circular on Sun Jul 01, 2018 2:19 pm, edited 1 time in total.
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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by Fiver »

I agree Circular. The expertise and patience it takes to use a whole systems approach is probably beyond me. Especially this week.

I'm glad smarter people are on it!

I wonder if I can pose a related question that's bothering me thee days:

Once we have a full system model of AD and understand it much better do you think we'll come back to see that it is, in most cases, basically an apoe4 issue. I wonder if one could correct apoe4 somehow what % of cases would that prevent? (I'm guessing >50%.)

I think of it like this. I do some "restoration" on an old car. And sometimes I want to know exactly why it isn't running well because I like to appreciate the engineering. But sometimes I just want it fixed because I need to drive somewhere. So I find the problem and replace whatever wasn't working - the carb or fuel pump, for example. I never know exactly what was wrong with the part. But it works. And all the other problems go away.

I look at some of the studies that "fix" E4 with structure correctors or gene-editing/silencing and those cell cultures and mice recover fast.

....or maybe I'm just really impatient! :roll:
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Re: RE: Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by Stavia »

Fiver wrote:Hi circular. Holy cow. That is one long paper. I think I would need all day to really absorb it.

That's a very complex review of the web of networks and approaches for understanding and early detection. There is less about actual treatment options, for now or in the future.

As I read, I found myself growing impatient. Understanding and early detection are important, but then what?

It also made me wonder how accessible the personalized, systems-type medicine will be. Most patients struggle to get their family doctors to do the basics. How will patients access this complex, expensive stuff? It doesn't seem like our current healthcare system can handle personalized medicine for the masses.

Oh my, was that overly critical? Probably just my mood today. :?
Circ I completely agree. It will be hideously expensive and will create even more of a two tier society with a privileged few (mostly in the USA) having access. Most of the worlds population cannot even access/afford basic dental care. And dont get me started on the widespread ignoring of the dismal state of our environment/planet.

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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by circular »

I completely get where you're coming from (deleted the News app from my phone yesterday because I just can't take it anymore ... it has to be harder for me to get the news, more hoops, less incentive, less I know, better off I am with all the things I have no control over).

At the same time, taking the loooooong view, isn't the idea that bioinformatics will be able to reduce the complexity to something eventually established as evidence-based science and protocol and applicable using a kind of computerized decision tree? And doesn't technology often also eventually reduced prices once commoditization sets in? I agree it's a bit of a dream world, and the haves will always get something others don't, or more of something others have little of (have since the beginning of time), which totally sucks, but either we embrace the rigors of science or throw it all out. I imagine there will be tiers of personalized medicine that rely on various levels of complexity for different costs. We already have tiers of medicine. I think the problem is less technical and more political.

Technology has brought us to these unavoidable complexities and it is the only way forward. NASA doesn't give up new missions deeper into space because it's complicated. I would also argue that the functional medicine world is causing patients - including me - to spend a lot of non-disposable income unnecessarily, going more with theory than evidence, all the while supporting patients' belief that if they don't do this or that they're doomed to horrible diseases.

I still need to actually read the paper (if I can find that much time at once), but I got the feeling it could be very useful to our forum members to help people appreciate the complexity and the need to keep the big picture in mind until we know more?

Just kind of thinking out loud before dashing out to an appointment. Will probably disagree with myself somehow in the car :D
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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

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I could also suggest a better argument than my last one for dismantling NASA altogether and redirecting their money to food distribution. If we can fly through Jupiter’s rings you’d think we could sort out how to feed our planet’s people, huh?
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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by Fiver »

I get your point. And, really, I should be on the side of slow, careful science and appreciating the complexity.

For some reason I just feel impatient. Maybe it's being involved in caring for my mom. Maybe it's the news on TV. I think I have taken the (selfish) perspective of mostly caring about what happens to bring a treatment forward in the next ten years or so. That is one long paper. Wow. And I feel some urgency. And I've latched on to E4 "fixes".

We need both short- and long-term approaches, of course!
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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by Stavia »

Ok here's the abstract.
Its a new set of European based organisations aiming to do at large scale what Bredesen has done. Collect, systematise, analyse and integrate everything possible (biomarkers, imaging, functional testing etc etc) in a systems approach aimed at identifying drivers and possible interventions for AD and other neurodegenerative diseases.
Big dreams. Big data. Gonna need Big money.

"Abstract

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD).
The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND".



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Re: 'Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology'

Post by NF52 »

circular wrote:At the same time, taking the loooooong view, isn't the idea that bioinformatics will be able to reduce the complexity to something eventually established as evidence-based science and protocol and applicable using a kind of computerized decision tree?
Stavia wrote:It will be hideously expensive and will create even more of a two tier society with a privileged few (mostly in the USA) having access. Most of the worlds population cannot even access/afford basic dental care.
After reading the word "omics" a few months ago and wondering "Why does everybody seem to know the meaning of this word that I've never seen before?" I decided to look for a good explanation. I found this free article, listed as an "Editor's Choice" in the American Journal of Epidemiology from 2014. Also found a new "-omics": exposomics: the study of everything we are exposed to in our lifetimes (see below). {Very hard not to read that as "Expose-comics"--an example of my childhood exposure to comics taking over my brain!}

With apologies for the length (but maybe saving folks having to read the whole thing!) here are a few excerpts that I think capture what Circ (and I) hope will be the power of precision medicine using "omics", as well as Stavia's question of moral hazard in privileging health of first-world over third-world (or rich over poor) peoples. [Emphasis added; citations deleted.]
Omics is an English-language neologism that refers to a field of study in biology ending in “-omics.” Examples include genomics, proteomics, and metabolomics. A related suffix (-ome) is often used to refer to the objects of study in these fields (e.g., the genome, proteome, or metabolome). The research area of -omics focuses on the collective characterization and quantification of large numbers of biological molecules that translate into the structure, function, and dynamics of an organism...These emerging fields of scientific inquiry (e.g., microbiomics and exposomics) have several features in common, including the use of biomarkers to determine exposure, effects of exposure, and susceptibility factors; the use of technologies that produce large amounts of data; and the use of data-mining techniques to identify statistically significant associations .

Collaborative research teams and individual scientists have considered ways to integrate genetic information with social and contextual information in epidemiologic studies. Several authors have called for new research paradigms in epidemiology that more adequately take into account different levels of analysis at the molecular, individual, and societal or group levels...

[E]nthusiasm about the power of genomics to determine disease etiology...has led to a tendency to view associations with genetic factors as causal and associations with factors related to the broader social, cultural, or behavioral context as noncausal ... there is no a priori reason to assume that causes found at the genetic or molecular level are any more significant than causes operating at another level, such as social factors...An emerging paradigm of disease prevention is the identification and modification of environmental risk factors among persons who are susceptible to disease because of their genotype.[/b]....
These scientific challenges require systematic approaches to acquire and utilize information about the timing, intensity, and duration of exposures and associated biological responses and health outcomes ...

The exposome concept takes into account the full spectrum of possible exposures (diet, dietary supplements, food additives, pesticide residues, microbial organisms and infections, geophysical exposures, environmental pollution, smoking, alcohol consumption, exercise, infections, vaccinations, occupational exposures, consumer products, therapeutic drugs, severe stress, etc.), the timing of exposures, and acute and chronic responses to exposures. In contrast to the genome, the exposome is highly variable and dynamic and evolves throughout the lifetime of an individual.

...In the not-too-distant future, it may be possible to use this information to prevent or treat disease... [M]oving forward requires greater awareness of the exposome paradigm and a willingness to explore and think in novel ways...Longitudinal studies are needed that include sizeable numbers of persons of various ages who are healthy or have preclinical or clinically diagnosed illness. This will help to rule out reverse causation and facilitate the identification of metabolomic and proteomic markers of preclinical disease and disease progression.

Finally, efforts to develop, combine, and analyze large, complex data sets should be guided not only by scientific considerations but also by ethical considerations, such as individual privacy and confidentiality of health information, maximizing benefits in an equitable fashion, and policy considerations related to how best to utilize finite resources for health research. An example of the latter is the ongoing policy debate over how many public resources should be spent on genomics versus traditional epidemiologic approaches for preventing disease and protecting health... Despite the expense and complexity, however, -omics research is likely to become an increasingly important part of epidemiologic studies in the foreseeable future.
Toward a Road Map for Global -Omics: A Primer on -Omic Technologies
4/4 and still an optimist!
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