Alzheimers Disease: The Amyloid Hypothesis vs The Mitochondrial Hypothesis

[Gert van der Hoek]

The cause of Alzheimer's disease is poorly understood.The disease process is associated with plaques and tangles in the brain. A probable diagnosis is based on the history of the illness and cognitive testing with medical imaging and blood tests to rule out other possible causes. Initial symptoms are often mistaken for normal ageing. Examination of brain tissue is needed for a definite diagnosis. Currently no treatment is available.

Mainstream science is focussing on amyloid plaques and tau proteines as a possible cause. Some mavericks point to mitochondrial dysfuncion as a trigger for development of AD. Until now all drug trials related to the amyloid hypthesis have failed, despite huge investments. Hardly any funding for trials working with the mitochondrial hypothesis.

Swerdlow c.s. defend the mitochondrial hypothesis. In their paper published in 2013, they explain the current state of both hypotheses.


The Alzheimer's Disease Mitochondrial Cascade Hypothesis: Progress and Perspectives

Abstract

Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it.

We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it.

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[Gert van der Hoek]

Do we all have Alzheimer's completely wrong? This man says yes

Science Friday
May 03, 2015


Throughout his career, Duke University neurology professor Allen Roses has challenged what for decades has been the prevailing orthodoxy in Alzheimer?s research: Namely, the ?amyloid hypothesis,? which suggests that a protein called beta-amyloid clogs up the brain, killing neurons and causing the dementia associated with Alzheimer?s disease.

?Beta-amyloid is the result [of Alzheimer?s], rather than a cause,? he says.

For more than 20 years, Roses, 72, has pursued a hunch that dementia in Alzheimer?s patients stems from an inability in the brain to metabolize energy sources, such as glucose and oxygen. The trigger, he argues, is variations in two genes ? ApoE and TOMM40 ? which ultimately inhibit mitochondria from supplying energy to neurons, causing them to die. A growing body of published literature supports his theory, Roses says, but by and large, he ?has been totally ignored? by the field.

Pugnacious and prickly when crossed, but not lacking a sense of humor (he names his startups after red wines), Roses has moved from academia to industry and back again, survived funding droughts, and even fronted his own money in order to establish his counter-theory to what he has called the ?amyloid cult.?

Mitochondria are critical for the normal functioning of neurons, which need energy to communicate with each other. But unlike other cells in the body, neurons can?t reproduce. Consequently, when mitochondrial motors slow down ? as they do with age ? they deprive neurons of vital fuel. As energy-starved neurons die with nothing to replace them, the brain?s cognitive functions also deteriorate.

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[Gert van der Hoek]

A research team worked with transgenic mice, all got Alzheimers. They could protect the mice with a dietary intervention: restricting calories by restricting carbohydrates. In other words: an "Atkins like" diet could protect against Alzheimers. In mice.



Caloric restriction attenuates β-amyloid neuropathology in a mouse model of Alzheimer?s disease

Nutrient composition in the CR diet was adjusted so that CR was achieved by selectively reducing the carbohydrate content of the diet while consumption of protein, fat, cholesterol, vitamins, and minerals was identical.

see also Tabel 1

CR animals consumed 42% less carbohydrates, however, accounting for a 30% decrease in total caloric intake.

When Tg2576 mice were examined for AD-type neuropathology at 12 months of age, we found that 9 month CR treatment almost completely prevented cortical and hippocampal AD-type amyloid plaque development (Fig. 2A and B) relative to animals in the AL-fed group. Consistent with this evidence, we noted commensurately lower concentrations of amyloidogenic Aβ1-40 and Aβ1-42 peptides in the neocortex and hippocampus as evaluated by ELISA assay, relative to AL-fed controls (Fig. 2C).

Our studies support the hypothesis that low carbohydrate CR may prevent AD-type amyloid neuropathology

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[Gert van der Hoek]

Mitochondria provide the energy for you cells, including the cells of your brain. If the mitochondria have difficulties to metabolize glucose - the mitochondrial hypothesis - this can cause the cognitive problems we know as Alzheimers Disease. There is some research and there are case reports, saying fat, and especially Middle Chain Fats - Coconut oil - can help to feed the brain, it is easier for the defective mitochondria to metabolize.


The role of dietary coconut for the prevention and treatment of Alzheimer's disease: potential mechanisms of action.


Abstract


Coconut, Cocos nucifera L., is a tree that is cultivated to provide a large number of products, although it is mainly grown for its nutritional and medicinal values. Coconut oil, derived from the coconut fruit, has been recognised historically as containing high levels of saturated fat; however, closer scrutiny suggests that coconut should be regarded more favourably. Unlike most other dietary fats that are high in long-chain fatty acids, coconut oil comprises medium-chain fatty acids (MCFA). MCFA are unique in that they are easily absorbed and metabolised by the liver, and can be converted to ketones.

Ketone bodies are an important alternative energy source in the brain, and may be beneficial to people developing or already with memory impairment, as in Alzheimer's disease (AD). Coconut is classified as a highly nutritious 'functional food'. It is rich in dietary fibre, vitamins and minerals; however, notably, evidence is mounting to support the concept that coconut may be beneficial in the treatment of obesity, dyslipidaemia, elevated LDL, insulin resistance and hypertension - these are the risk factors for CVD and type 2 diabetes, and also for AD.

In addition, phenolic compounds and hormones (cytokinins) found in coconut may assist in preventing the aggregation of amyloid-β peptide, potentially inhibiting a key step in the pathogenesis of AD. The purpose of the present review was to explore the literature related to coconut, outlining the known mechanistic physiology, and to discuss the potential role of coconut supplementation as a therapeutic option in the prevention and management of AD.


PubMed


Memory loss associated with Alzheimer's reversed: Small trial succeeds using systems approach to memory disorders



In the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants displayed subjective or objective improvement in their memories beginning within three to six months after the program’s start.

The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer's Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.

Science Daily