The Toxicity of Amyloid β Oligomers

Posting this link to a free full text paper as I may forget it.

There is a useful section on the way curcumin helps prevent aggregation.

I think you also need to be aware that  Alzheimer’s Disease Linked to Diabetes

New Biomarker in the Blood May Help Predict Alzheimer’s Disease

New Biomarker in the Blood May Help Predict Alzheimer’s Disease
This new research is interesting as we've known for some time that the earliest signs of Alzheimer's can be detected up to 25yrs prior to diagnosis and it can lay dormant for most of that time.

This new research, linking earlier onset to higher ceramide levels, gives us the chance to see if lowering ceramides may delay onset.

MAGNESIUM deficiency INCREASES ceramide production.
There are lots of online calculators enabling you to check your diet at least meets the RDA for magnesium for your age/sex.

Magnesium absorption from food/water is less in vitamin D deficient people.
CityAssays Vitamin D Blood Spot test £25 enables you to check if 1000iu/daily/D3 per 25lbs weight raises your vit d3 status to 125nmol/l ~ 50ng/ml the level at which Vitamin D is most effective as an effective anti-inflammatory agent.

Ceramides are potent proinflammatory agents so people with higher vitamin D, magnesium, omega 3 and melatonin levels will be better able to deal with them.

If indeed it turns out to be the case that higher inflammatory ceramides are the driving force for Alzheimer's oneset then maintaining an effective reserve of natural anti inflammatory agents is simply common sense.

Preventing Alzheimer’s Disease?

I was motivated to write this reply to this post on another blog Preventing Alzheimer’s Disease?
which was written in response to the post by Mercola.

Astaxanthin: A Rising Star in Alzheimer's Prevention

I'll deal with what I think are the most likely strategies to preventing or delaying the onset of demetia in the next blog probably in response to Susan Graig's next post.

Well I hope the next post is a little more constructive and helpful to people who come to this blog hoping to find some sensible evidence based suggestions that may enable them to delay the onset of Alzheimer's or other dementias.

Mercola has provided a link to his source of statistics and I while using the upper figures from the ranges provided isn't distorting them unduly. Bear in mind Mercola has had several previous run ins with the FDA and doesn't have many friends in consensus medical opinion so ALL his online statements HAVE to be checked by his legal team before he can write anything. Only AFTER they have been double checked to see if they would stand up to legal scrutiny is he permitted to post. 

I think the one in four people being affected by Alzheimer's includes the relatives carer's and other close family. I'm sure everyone with an Alzheimer's relative is affected by that and the stress it imposes on the family and friends. 

I think your claim that we are living longer healthier lives is mistaken. Sure we may at the moment be living longer but surely not healthier lives. I don't know how many people you know aged 70 but try asking how many medications they are taking and what side effects they are experiencing? Sure I know a lot of blokes my age with Prostate cancer and while they certainly are still alive it's not the same quality of life that they experienced before treatment. Try asking how many are on statins and what the side effects of those are and any reasonable person would question if the trade off between the claimed risk reduction and the actual side effects they are experiencing is actually worth it is certainly debatable. Early detection of many conditions now doesn't necessarily lead to any reduction in all cause mortality but certainly leads to increased medical costs, treatments and other  iatrogenic consequences.  

While it is true that 10% of Alzheimer's is attributed to genetic predisposition I think it would have been better if you had pointed out this is mainly through the maternal DNA so people whose fathers but not mothers had AD can ignore that potential risk factor. While it may be different in the USA, in the UK I'm not sure that most people appreciate that the genetic predisposition for AD is generally through the maternal side. While genes certainly load the gun it's still environmental/dietary factors that pull the trigger, so even if your mother did get AD and you have had your DNA checked and found you  carried the risk that still does not mean there is absolutely nothing you could try to prevent or delay onset of AD. 

You will have to apply a bit of common sense and have an element of luck but I think it's simply untrue to state that 90% of Alzheimer’s cases are sporadic, meaning the disease occurs for no apparent reason. 

We know what the basic risk factors for AD are and we know roughly (though I accept not all the dots are as yet connected) how this impacts on disease initiation therefore I contend that most of the suggestions Mercola makes are sufficiently evidence based to be worthy of investing some time examining the evidence he uses and which are also supported by papers listed at Pubmed. 

We have to take Alzheimer's incidence very seriously in the light of the explosion in obesity and diabetes. These conditions predispose people to increased risk of dementia so it shouldn't be hard to work out that AD incidence will inevitably also increase.

Therefore to do everything possible to reduce hyperglycaemia and conditions that result from raised levels of inflammation is simply common sense.  

There was a recent report of a 68 yr old woman on being given an Alzheimer's diagnosis immediately walking in front of a train, irrespective of whether this was a direct result of knowing the diagnosis or just a consequence of the condition (obviously we'll never know)  we should not give people the impression an Alzheimer's diagnosis is a fate worse than death and that pharmaceutical drugs are the only or even the best way of managing this dreadful condition. We ought be talking about The Myth of Alzheimer's, What You Aren't Being Told About Today's Most Dreaded Diagnosis  Aging with Dignity; Aging with Hope

Resolving controversies on the path to Alzheimer’s therapeutics

Resolving controversies on the path to Alzheimer’s therapeutics
The full text of this article is available at the link.
It's interesting to see how the research has progressed and where it may be going.

I found the time line of Alzheimer's research interesting as well as chart showing the Hypothetical time course of AD with the stages at which interventions Clinical trials are applicable. Confirms my opinion we need to act before symptoms of any kind are apparent and the distinction between normal ageing and Alzheimer's is not as clear cut as some would like to portray.

Mitochondria, Amyloid β, and Alzheimer's Disease

Mitochondria, Amyloid β, and Alzheimer's Disease
Nice free full text online paper that fits in with much of what I've been thinking about.

for those who are interested in learning how to ensure an ongoing supply of new healthy mitochondria this paper has some practical suggestions.
Mitochondrial Energetics and Therapeutics

Melatonin in Mitochondrial Dysfunction and Related Disorders

I should perhaps give a warning that these are quite heavy going papers so don't expect to understand every word initially.

Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet

Alzheimer's disease is a devastating disease whose recent increase in incidence rates has broad implications for rising health care costs.
Huge amounts of research money are currently being invested in seeking the underlying cause, with corresponding progress in understanding the disease progression.
In this paper, we highlight how an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency in dietary fats and cholesterol, may lead to the development of Alzheimer's disease.
A first step in the pathophysiology of the disease is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport.

This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function.
Over time, a cascade response leads to impaired glutamate signaling, increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, apoptosis.
Other neurodegenerative diseases share many properties with Alzheimer's disease, and may also be due in large part to this same underlying cause

For those who find reading full text papers difficult (why don't they use words more easily understood) they provide this useful summary of the main points.

Learning points
1. The amyloid-β present in Alzheimer's plaque may not be causal, since drug induced suppression of its synthesis led to further cognitive decline in the controlled studies performed so far.

2• Researchers have identified mitochondrial dysfunction and brain insulin resistance as early indicators of Alzheimer's disease.

3• ApoE-4 is a risk factor for Alzheimer's disease, and ApoE is involved in the transport of cholesterol and fats, which are essential for signal transduction and protection from oxidative damage.

4• The cerebrospinal fluid of Alzheimer's brains is deficient in fats and cholesterol.

5• Advanced glycation end-products (AGEs) are present in significant amounts in Alzheimer's brains.

6• Fructose, an increasingly pervasive sweetening agent, is ten times as reactive as glucose in inducing AGEs.

7• Astrocytes play an important role in providing fat and cholesterol to neurons.

8• Glycation damage interferes with the LDL-mediated delivery of fats and cholesterol to astrocytes, and therefore, indirectly, to neurons.

9• ApoE induces synthesis of Aβ when lipid supply is deficient.

10• Aβ redirects neuron metabolism towards other substrates besides glucose, by interfering with glucose and oxygen supply and increasing bioavailability of lactate and ketone bodies.

11• Synthesis of the neurotransmitter, glutamate, is increased when cholesterol is deficient, and glutamate is a potent oxidizing agent.

12• Over time, neurons become severely damaged due to chronic exposure to glucose and oxidizing agents, and are programmed for apoptosis due to highly impaired function.

13• Once sufficiently many neurons are destroyed, cognitive decline is manifested.

14• Simple dietary modification, towards fewer highly-processed carbohydrates and relatively more fats and cholesterol, is likely a protective measure against Alzheimer's disease.

I've added the numbers so I can comment on them.
Re 1 We need to learn a lot more about Protein folding and if you want to help this research you can by downloading the computer program FOLDING HOME Whenever your PC is left on it works on this research project quietly in the background. My PC has completed 611 projects for them and I don't notice it working in the background and it's easy to pause if you want to play a game that requires 100% of you PC computing power.
2. Mitochondrial dysfunction is at the root of diabetes, metabolic syndrome and all that flows from these conditions. We can create new fully functional mitochondria by A)Exercise even modest exercise will help. B)Intermittent Fasting this does not have to mean a 24hr fast, Not eating between meals. Having just 2 meals a day, eating those 2 meals within 5hrs so there is 19hrs without any food. (gives a chance for fat burning) C) A Ketogenic diet. Less carbohrate more fat particularly coconut oil and Medium Chain Triglyceride oil. These are used as a substitute for glucose and metabolised straight away rather than being stored.
3.Apolipoprotein E4: A causative factor and therapeutic target in neuropathology, including Alzheimer’s disease this full text paper will help you better understand the role of ApoE4.
4~ So we need more fats of the type that are known to be used in the brain, hence Coconut Oil, MCT, Butter (pasture fed higher omega 3) more OMEGA 3 fish oil less or no industrial seed oils like such as corn, soybean, safflower, sunflower and cottonseed oil and any commerially prepared food made using those pro inflammatory omega 6 oils.
5~ AGE's are the brown parts when foods are roasted/fried grilled and beginning to burn. Fewer roasts/barbeques/grills and more soups, stews and casseroles. Don't fry your bacon to a crisp. It's fine if it'slightly underdone. Liver tastes best if pink in the middle IMO.
6~ We shouldn't add HFCS to anything let alone baked items. This is particularly so when you buy baked items. It's just amazing where you find HFCS, corn syrup these days.
7~ For every brain neuron we have 10 times more astrocytes. Apart from providing ketones to keep neurones from starving should glucose sources get low, they also regulate blood flow through the brain. It's arguable disruption of brain blood flow is involved in MS. To keep astrocytes healthy they need feeding. Fat and cholesterol, bacon and eggs for breakfast fried in coconut oil. My choice for healthy astrocytes with a tsp of omega 3 fish oil.