You understood well. I found some citations on the website of Stephanie Seneff : e.g. book from Dr. Duane Graveline: Lipitor: Thief of Memory. He writes about common side effect of statins - memory dysfunction. Statins likely impact Alzheimer's is in their indirect negative effect on the supply of fatty acids and antioxidants to the brain. Another way in which statins may promote Alzheimer's is by crippling the ability for cells to synthesize antioxidant coenzyme Q10, as coenzyme Q10 shares the same metabolic pathway with cholesterol.

Do you mean if it happens in non-pathological conditions?

Is aggregation a normal process?

Suspect you have some thoughts on this already! From a general standpoint, it seems to me that cell architecture and biology has likely evolved from a system based upon the organisation of self-associating elements (e.g. base pairing, or phospholipids in membranes) and that ordered aggregation of proteins is one such fundamental process. Various examples of this have been advantageous and are conserved with modifications. However it comes with risks: e.g. toxic gain of function through conformational change, high stability impeding turnover. How far any such ordered aggregation event is ‘normal’, ‘inevitable but tightly controlled’, ‘allowed’, ‘playing a physiological role’, ‘toxic’ is likely to be highly modifiable but can be addressed to some extent by smart cell biology experiments. What’s your take when it comes to where tau and Abeta are on this spectrum?

I read, that it has been belived, that amyloid-beta is the principal cause of Alzheimer. But some researchers think, it is rather a protective device against it. Amyloid beta should have the unique capability of stimulating the productio of lactate dehydrogenase, which promotes the breakdown of pyruvate into lactate. Lactate is then trasported from the astrocyte to a neigboring neuron to enhance its energy suppz, thus reducing its dependence on glucose. Amyloid beta is believed to be produced as a consequence of enviromental oxidative stress due to an inadequate supply of fats and cholesterol from the blood - a result of low-fat diet or statins.

My take is that the 'pathology' of AD is a physiological response to metabolic failure

George

What exactly do you mean? Inadequate supply of the neurons with fatty acids, which I mentioned or something else?

Energetics

Brevity is admirable, but can be ambiguous! Do you mean you regard these aggregates as epiphenomena of a more generalised process that includes a failure of protein homeostasis? If so how does this allow for genetic predispositions to Abeta overproduction causing disease?

Perfectly happy with that, but unclear where it leads us with this question. Are you saying that low free energy states will be directly pathological, or that a dysfunctional/ageing biological system loses the ability to handle relatively metastable states?

Sincerely, this discussion has some aspects that seem to me a bit 'hermetic" and which are not entirely clear for my mentality of clinical neurologist. For example, I cannot well understand what he said Ludmilla Paskova: "Amyloid beta is believed to be produce as a consequence of environmental oxidative stress due to an inadequate supply of fats and cholesterol from the blood - a result of low-fat diet or statins". I believe was known that statins do not exert a preventive action for AD, but I did not know you could even have a negative effect. I misunderstood?

You understood well. I found some citations on the website of Stephanie Seneff : e.g. book from Dr. Duane Graveline: Lipitor: Thief of Memory. He writes about common side effect of statins - memory dysfunction. Statins likely impact Alzheimer's is in their indirect negative effect on the supply of fatty acids and antioxidants to the brain. Another way in which statins may promote Alzheimer's is by crippling the ability for cells to synthesize antioxidant coenzyme Q10, as coenzyme Q10 shares the same metabolic pathway with cholesterol.

Thank you for your very interesting answer about a rather controversial topic. Generally, specialists cardiologists think that neurologists are exaggerated to be quite doubtful on statin therapy!

My take on it is that it is a true pathology of the brain, not necessarily a result of deficiency in bioenergetics or metabolism (although these can be contributing factors). You expect to see damage and deficiencies with age, and we do see dementia and normal memory loss, etc in these individuals. But that is not all we see in neurodegenerative diseases. We see specific areas consistently targeted and damaged. With Tau and Abeta, these may occasionally aggregate within the cell and are eliminated normally, but something seems to specifically trigger them in AD.

It occurs to me that there is a virus or prion-like disease that spreads in brain, and that it can cause different pathology depending on where it begins (AD = limbic system, HD = basal ganglia, PD = substantia nigra). Do we see the cellular responses we expect to see with aging, atrophy, and damage? Yes. But it seems much more likely that these areas are specifically targeted. Perhaps there is a viral component that is being missed? There are known endemic viruses that affect the nervous system specifically (eg: Herpes viruses). These may ultimately be the contributing factor/trigger that is being missed.