Inflammation and ageing are risk factors of multiple diseases such as Alzheimer or Parkinson’s diseases or cardiac infarct. Theses diseases share a common biological strait: the Warburg’s effect.

Schwartz, L., Henry, M., Alfarouk, K. O., Reshkin, S. J., Radman, M. (2021). Metabolic Shifts as the Hallmark of Most Common Diseases: The Quest for the Underlying Unity. International Journal of Molecular Sciences, 22(8), 3972.


Aloïs AlzheimerWarburg in Alzheimer’s disease

Alzheimer’s disease was first described by the German neurologist Aloïs Alzheimer (1864-1915). Alzheimer was a decent physician fighting against implementing inhuman policies at the asylum. He required that his staff treat patients humanely, interact and frequently talk with them, and provide therapeutic baths for them. Previously, patients in an asylum received little care, leading to the frequent use of the isolation room.

He studied the case of a woman named Augusta Deter. This 51-year old patient had strange behavioral symptoms, including a loss of short-term memory. Augusta Deter was a victim of the politics of the time in the psychiatric community; the Frankfurt asylum was too expensive for her husband. Herr Deter made several requests to have his wife moved to a less expensive facility, but Alzheimer intervened in these requests. Augusta Deter remained at the Frankfurt asylum, where Alzheimer had made a deal to receive her records and brain upon her death.

On April 8, 1906, Augusta Deter died, and Alzheimer had her medical records and brain brought to Munich where he was working in Kraepelin's laboratory. With two Italian physicians, he used Bielschowsky's staining techniques to identify amyloid plaques and neurofibrillary tangles. These brain anomalies would become identifiers of what later became known as Alzheimer’s disease. Aloïs Alzheimer discussed his findings on the brain pathology and symptoms of presenile dementia publicly on 3 November 1906, at the Tübingen meeting of the Southwest German Psychiatrists. The attendees at this lecture seemed uninterested in what he had to say. The lecturer that followed Alzheimer was to speak on the topic of “compulsive masturbation”. The audience was so eagerly waiting this conference that they sent Alzheimer away without any questions or comments on his discovery of the pathology of a type of senile dementia.

Following the lecture, Alzheimer published a short paper summarizing his lecture; in 1907 he wrote a more substantive paper detailing the disease and his findings. The disease would not become known as Alzheimer's disease until 1910, when Kraepelin named it so in the chapter on “Presenile and Senile Dementia” in the 8th edition of his Handbook of Psychiatry.

Today, there is no treatment for Alzheimer’s disease nor is there any real hope in the foreseeable future. The best we have to offer is supportive care and psychological counsel for the patient and his family. The industry tried to develop antibodies targeting the amyloid plaques, but without any positive result. Having failed, they now try to market the same drugs in the patients at high risk of developing dementia. This is a marketing effort for financial gains for pharmaceutical industry, not medicine.
The lack of a reliable animal model has limited much needed research to find a cure for Alzheimer’s disease. Instead of waiting months for mice to age and become senile to test treatments being carried out, the researchers have tried to insert genes into the genome of mice. The mice are transgenic.

There are rare cases of hereditary Alzheimer’s disease. The patient like Augusta Deter suffered from Alzheimer’s disease before the age of 60. The researcher insert the defective gene, which cause this variant of Alzheimer’s disease into the genome of a mouse. Like Augusta Deter, the transgenic mouse becomes senile when a few weeks old.
For the most common form of Alzheimer’s disease which arise almost at random among the elderly, no gene has been demonstrated to be the culprit. We do not have any animal model for the most common Alzheimer’s disease. These transgenic and expensive mice (each transgenic mouse costs around $300) allow testing of drugs. Treatment may work in transgenic mice, but it always fails in human. Today, the treatment of Alzheimer’s disease is similar to the one at the epoch of Aloïs Alzheimer. No real progress has been made in a century.

It has been known for years that trauma is a risk factor for Alzheimer’s disease.
Mortimer, J. A., Van Duijn, C. M., Chandra, V., Fratiglioni, L., Graves, A. B., Heyman, A., Shalat, S. L. (1991). Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. International journal of epidemiology, 20(Supplement_2), S28-S35.

Head trauma causes inflammation of the brain which paves the way to Alzheimer’s disease. Veterans having experienced the blast of an explosion or American football players are at risk of senility in middle age. To confirm the link between inflammation and Alzheimer’s disease, we subjected mice to repetitive trauma. Several times a day, the head of the mouse receives a drop of small lead ball. The mouse that experienced the most frequent trauma developed both Alzheimer and Parkinson. It may seem barbaric but it is the only way to get Alzheimer’s disease in mice. Treatment can be tested on animals who have Alzheimer’s disease.
Nogueira, M. L., Hamraz, M., Abolhassani, M., Bigan, E., Lafitte, O., Schwartz, L. (2018). Mechanical stress increases brain amyloid β, tau, and α-synuclein concentrations in wild-type mice. Alzheimer's & Dementia, 14(4), 444-453.


Restriction of the food intake of adults, i.e., caloric restriction, seems to decrease the incidence of Alzheimer’s disease. For a 30% decrease in the amount of calories over a long period of time, the risk of inflammation, cancer and Alzheimer drops significantly.
Van Cauwenberghe, C., Vandendriessche, C., Libert, C., Vandenbroucke, R. E. (2016). Caloric restriction: beneficial effects on brain aging and Alzheimer’s disease. Mammalian genome, 27(7-8), 300-319.


Like in cancer or in inflammation, the patient is more frequently obese and diabetic. Low-carb diet decreases the risk of senility. In Alzheimer, like in cancer and inflammation, there is a rewiring of the metabolic fluxes. But the major fuel is different. For cancer cells it is glucose, whereas for neurons, it is lactic acid. The difference in fuel explains the biology. In cancer, there is cell proliferation, while in Alzheimer’s disease there is cell death.

The brain has the highest energy consumption of the body (around 20% of the body oxygen and 25% of the glucose) while representing only 3% of our body’s mass. Neurons feed on lactate released by the glial cells. When you have inflammation of the brain, the glial cells are under pressure. They express the Warburg phenotype and secrete more lactic acid that is taken up by neurons. This increase uptake of lactic acid results in intracellular acidosis of the neurons.

To perform their normal physiological functions, cells must maintain the intracellular pH (pHi) within the physiological range. The value of the pHi is closely associated with intracellular enzyme activity, cytoskeleton component integration, and cellular growth and differentiation rates. Acidic intracellular pHi of the neuron is a consequence of the excessive secretion of lactic acid by the surrounding glial cells and results in cell death. In cancer, the alkaline pH results in cell proliferation. In neurodegenerative diseases, the acidic pH results in cell death. They are both a consequence of the Warburg’s effect.
Schwartz, L., Peres, S., Jolicoeur, M., da Veiga Moreira, J. (2020). Cancer and Alzheimer’s disease: intracellular pH scales the metabolic disorders. Biogerontology, 1-12.