On 21 September each year, in the World Alzheimer’s Dayone has the impression of starting over: while 55 million patients await, with their families, a possible therapy against the disease of the centurythe search for drugs and explanations remains at a dead end.
The most accredited hypothesis of the last 15 years, which saw the accumulation of beta-amyloid protein on neurons as the main cause of the disease, may have been the result of a manipulation and in any case did not lead to effective treatments. Even the much-vaunted aducanumab, the drug approved in the US in 2021 that eliminates amyloid plaques, does not seem to give any benefits in spite of the risks for those who take it.
Autoimmune hypothesis. The unconventional hypotheses are welcome then, which try to explain the disease in another way. And if by hypothesis Alzheimer’s wasn’t a brain disease, but a disease of the immune system within the brain? The idea proposed by the scientists of the Krembil Brain Institute in Toronto (Canada) starts from considering beta-amyloid not a protein produced under abnormal (i.e. pathological) conditions, but a molecule normally present in the brain as part of the immune system.
If trauma or bacterial infection occurs, amyloid beta is ready to play defense. But – this is the hypothesis also summarized on The Conversation – at this point a kind of misunderstanding occurs. The lipid coating of bacteria resembles that of nerve cells. Beta amyloid does not distinguish between the two different membranes and targets the wrong target: not the invading bacteria but the neurons it was supposed to protect.
The search for cures. Neurons suffocated by amyloid plaques lose functionality, and this progressive cell death effects cognitive decline and other symptoms on behavior, mood and personality typical of Alzheimer’s disease. Seen in this light, beta-amyloid self-sabotage resembles an autoimmune reaction as seen in other diseases caused by runaway autoantibodies.
For now, drugs used against known autoimmune diseases, such as rheumatoid arthritis, have not been shown to be effective against Alzheimer’s. But by continuing to look in this direction (ie by hunting for regulators of the immune response), we may one day see a way forward. The hypothesis, detailed last April in the magazine ofAlzheimer’s Associationit is not the only “fresh” idea on the causes of the disease.
In the heart of the cells. In addition to the theory of autoimmune disease – in the past also advanced for another neurodegenerative disease: Parkinson’s – another very original hypothesis that has recently emerged is that Alzheimer’s is a disease of the mitochondria, the power plants of cells (including those of the brain). ), which convert oxygen and glucose into energy.
Based on a study just published in Molecular Psychiatry, a newly discovered gene mutation in the mitochondria would be associated with a 20-50% higher risk of developing Alzheimer’s disease. The gene in question regulates the production of a small protein – called SHMOOSE – which if the mutation is present is inactivated. Since the “offending” mutation is found in about a quarter of the population of European origin, the discovery could represent an important addition to the (so far few) known genetic risk factors for Alzheimer’s.