Alzheimer’s disease and mitochondrial dysfunction

“Alzheimers’s is not a disease. It’s a complex outcome from the marriage of our genes with our environment, with our lifestyle.”[i]

We think of Alzheimer’s disease as a disease of the brain – we jokingly call it “Old Timer’s Disease” and hope that we never get it…

But what if Alzheimer’s disease were really a metabolic disease that happens to manifest primarily in the brain? What if this metabolic disease actually occurs all over the body, not just in the brain? What if we could actually diagnose it YEARS before it became manifest in the brain?

Many of us watched our parents decline into dementia, while their bodies stayed apparently healthy and robust until shortly before they died? We watched their minds slip away, memory by memory, logical thought by logical thought, until the only thing left was their worst fears, and their heartbreakingly healthy bodies.

And we wondered, in our secret hearts, whether this was the path we were also destined to tread … After all, maybe it was in our genes. We were told that the ApoE gene had a lot to do with our risk of developing Alzheimer’s, and the ApoE-4 gene was the very worst one, the one that carried the highest risk. And we were afraid…

And we despaired because we were told time and time again that there is no cure, there is only treatment of symptoms until they get so bad that we are forced into a nursing home, waiting for the grim reaper’s visit.

As recently as 2006 we ready in Nature Magazine: “much power is in the hands of governmental funding agencies and pharmaceutical companies throughout the world that set the budget for Alzheimer disease research. They can maintain the current pace and direction of research, or they can drive new ideas by increasing funding and allowing development of more risky approaches that may be associated with significant reward.”[ii] Nowhere in that issue is there mention of mitochondrial dysfunction or metabolic imbalances. We are still thinking that amyloid beta deposition and neurofibrillatory tangles are the whole story. The final paper in that issue is entitled: Alzheimer disease: progress or profit? How much is it going to cost us to care for these 90-year-old infants?

Sad commentary on the state of medicine, that we can only bemoan our lack of progress, and the lack of drugs to treat the symptoms. We are told over and over that by the year 2050 it is anticipated that we will be spending untold zillions of dollars to treat an elderly population which is relentlessly marching toward dementia.

In 2022 an article published on the Quest Laboratory website states: “In 2021, over 6 million Americans were estimated to have Alzheimer’s disease; this number is projected to increase to 14 million by 2060… The pathogenesis of Alzheimer’s disease has been attributed to neuronal degeneration caused by β-amyloid (Aβ)-containing extracellular plaques and tau-containing neurofibrillary tangles.” End of story. The rest of the article involves description of diagnostic tests and how to make diagnosis early. In the final analysis, the article states: “No pharmacological or non-pharmacological approaches are available to prevent cognitive impairment and dementia due to Alzheimer’s disease.” The article does mention modifiable behaviors – non-specific changes to diet, taking vitamin D, exercising – which “may delay the onset of overt dementia”. Not a very enthusiastic or exciting prospect, or much intimation of successful treatment. The treatment paragraph is called “management” and involves mostly drugs to treat the inevitable agitation, insomnia, restlessness and sometimes aggression that occurs when our minds are so clouded by disease that we revert to our base unfiltered behavior…

The final blow is here: “the United States Preventive Services Task Force has stated there are insufficient data on improved patient outcomes to recommend the utility of cognitive screening” – so don’t even bother to try to diagnose it early, since there is nothing we can do about it anyway.

How is it possible that we, the medical profession, have been so unaware of what our colleagues in research have been discovering and publishing for the last 20 years? It’s not as though this “new” information just appeared in the literature. It has been in publication since at least 2002 – and there are hints of the information even as early as the 1980s.[iii], [iv], [v], [vi]

What we learn first and foremost is that Alzheimer’s disease is a metabolic disease. The metabolic abnormalities found in the brain are not limited to the brain, but rather appear in every organ system and cell type of our bodies. Oxidative stress causing damage to mitochondria is described with increasing frequency in the literature.[vii] As early as 1984 we read about cortical abnormalities of glucose utilization. [viii]

In 2003 we read the suggestion that“As MCI [mild cognitive impairment] may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia.”[ix],

The refrain is picked up in the 20-teens: “Measurement of biomarkers “suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders… studies showing that antioxidant vitamin deficiency alone is sufficient to induce neurological deficits similar to those in AD… deficiency of vitamin E, one of the most important fat soluble antioxidants, caused dementia and other neurological symptoms with an increased risk of developing AD… and the addition of vitamin E could reverse the neurologic dysfunction”.[x]

Are these measurements of oxidative stress esoteric? Something that can only be done in a research lab? True, most of those measurements are not available through a conventional laboratory. But there are options. We can measure many of these research biomarkers through specialty functional lab testing like Genova Diagnostics[xi], Great Plains[xii], and many others. This testing is often at least partially covered by most insurance plans, and results help to guide recommendations for treatment.

We begin to read about mitochondrial dysfunction with ever-increasing frequency.[xiii] Since the brain has the second highest number of mitochondria in the body, it stands to reason that brain function would be affected, right after we find ourselves unable to get up out of a chair or walk a mile, or balance on one leg for 10 seconds.

Which brings us to the next question: what are mitochondria and why do we care how well they function?

Madeleine L’Engle in 1973 wrote A Wind in the Door[xiv], a story about a child whose mitochondria rebelled, wanting to live on their own and not be dependent upon the child in whose cells they lived. Alas, the child became progressively weaker, and his mitochondria progressively more dysfunctional, until finally Sporos, the leader of the rebellion, realized that they could not function independently of their child’s body, that “symbiosis” was a necessary condition of their existence.

We learn that our mitochondria were independent organisms, billions of years ago, until they began to live with us, when we first developed into multi-celled organisms. The original arrangement is lost to the dim reaches of history, although scientists are attempting to track the evolution through analysis of mitochondrial and bacterial DNA.[xv] In the end, the most likely explanation is that the mitochondria provide us with cellular energy (in the form of ATP), as long as we provide them with fuel (the molecules they need to produce that ATP, derived from the food we eat). It’s a good arrangement, as long as both sides keep their part of the bargain.

And there-in lies the difficulty. So long as we ate whole foods, not contaminated with pesticides and foreign chemicals, we were much more likely to die of accidents or old age, rather than chronic diseases like diabetes, heart disease, and cancer – and degenerative neurologic illnesses like Alzheimer’s.

At this point, the jury is still out, debating whether eating a healthy diet, avoiding exposure to chemicals, and training our bodies to move is going to prevent the development of chronic diseases. “Scientific opinion” would lead us to say that there is insufficient research to make a decision. Common sense would argue otherwise.


[ii] Alzheimer Disease Nature Medicine 12:7) July 2006:746

[iii] Hardy, J., Adolfsson, R., Alafuzoff, I., Bucht, G., Marcusson, J., Nyberg, P., Perdahl, E., Wester, P. and Winblad, B., 1985. Transmitter deficits in Alzheimer's disease. Neurochemistry international, 7(4), pp.545-563.

[iv] Brion, J.P., Couck, A.M., Passareiro, E. and Flament-Durand, J., 1985. Neurofibrillary tangles of Alzheimer's disease: an immunohistochemical study. Journal of submicroscopic cytology, 17(1), pp.89-96.

[v] Perl, D.P., 1985. Relationship of aluminum to Alzheimer's disease. Environmental health perspectives, 63, pp.149-153.

[vi] Foster, N.L., Chase, T.N., Mansi, L., Brooks, R., Fedio, P., Patronas, N.J. and Di Chiro, G., 1984. Cortical abnormalities in Alzheimer's disease. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 16(6), pp.649-654.

[viii] Foster, N.L., Chase, T.N., Mansi, L., Brooks, R., Fedio, P., Patronas, N.J. and Di Chiro, G., 1984. Cortical abnormalities in Alzheimer's disease. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 16(6), pp.649-654.

[ix] Rinaldi, P., Polidori, M.C., Metastasio, A., Mariani, E., Mattioli, P., Cherubini, A., Catani, M., Cecchetti, R., Senin, U. and Mecocci, P., 2003. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiology of aging, 24(7), pp.915-919.

[x] Torres, L.L., Quaglio, N.B., de Souza, G.T., Garcia, R.T., Dati, L.M.M., Moreira, W.L., de Melo Loureiro, A.P., de Souza-Talarico, J.N., Smid, J., Porto, C.S. and de Campos Bottino, C.M., 2011. Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease. Journal of Alzheimer's Disease, 26(1), pp.59-68.

[xv] Gray, M.W., 2012. Mitochondrial evolution. Cold Spring Harbor perspectives in biology, 4(9), p.a011403.