Alzheimer’s disease results in degeneration of neurons leading to irreversible cognitive decline. It is therefore a cerebral pathology. Except that today, a new study advances a rather unexpected hypothesis: the disease would find its origin … in the liver.
You will also be interested
[EN VIDÉO] Soon a blood test to detect Alzheimer’s disease? A blood test for Alzheimer’s disease that could be done at your doctor’s office would soon be possible.
And if the Alzheimer’s disease did not start in the brain but in the foie ? This is the daring hypothesis of a new study published on September 14 in the journal Plos Biology. For several decades, it has been generally accepted that the Alzheimer’s disease is caused in particular by the accumulation of peptide amyloid beta, or β-amyloid, which causes plaques to form between the neurones in the gray matter of cortex cerebral. These plaques, which are the most characteristic sign of the disease, lead to dysfunction of the connections between neurons and symptoms associated with dementia. « Until now, researchers did not know where ß-amyloid came from or why it got deposited in the brain. Explains John Mamo, professor at Curtin University in Australia and lead author of the study.
Misleading mouse models
From previous research has shown that protein ß-amyloid is made inside the brain in association with lipoproteins. Except that these studies rely on mouse models genetically modified to overexpress the production of amyloid in the central nervous system (CNS), which skews the results and does not correspond to the majority of human patients, say the researchers. Indeed, only the genetic forms of the disease involve a overproduction of ß-amyloid by the brain; in most cases it is only an abnormal accumulation.
The “blood-brain” pathway hypothesis
John Mamo and his colleagues therefore developed a new mouse model, where mice produce amyloid proteins not in the CNS but only in the liver. They then found that the mice suffered from the same brain buildup of β-amyloid as those producing the protein directly in the brain. According to this hypothesis of the “blood-brain” pathway, the lipoproteins transport β-amyloid to the brain where it would accumulate as a plaque. ” This “blood-brain pathway” is important because if we can manage the blood levels of amyloid lipoproteins and prevent their leakage into the brain, it opens up potential new treatments to prevent Alzheimer’s disease and slow memory loss John Mamo enthuses. Because it must be admitted, until now, molecules designed to prevent plaque formation or remove previously formed plaques have not resulted in clinical benefit to patients.
An anti-cholesterol drug against Alzheimer’s?
In particular, the researchers suggest that a suitable diet or drugs that lower the level of amyloid lipoproteins could reduce the risk or progression of the disease. Previous studies in mice have notably shown that a diet rich in saturated fatty acids strongly stimulates β-amyloid biosynthesis and secretion. One could therefore assume that to reduce its inputs in triglycerides would slow down transport to the brain. John Mamo also started a clinical test in humans based on the blood-brain hypothesis, using an old anti-cholesterol drug called probucol (withdrawn from the market in 1995 for lack of sufficient evidence on its effectiveness) and which inhibits the formation of lipoproteins in the liver. THE’clinical test, scheduled to last two years, plans to recruit around 300 subjects with mild dementia linked to Alzheimer’s disease. She will examine whether the administration of probucol significantly reduces cognitive decline.