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Alzheimer's disease would be contagious

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Recent work also suggests that Alzheimer's disease could, under certain conditions, be transmitted between individuals.

More than 50 dementias resulting from neurodegenerative diseases have been identified to date, with Alzheimer's disease being the most widespread. It is now estimated that approximately 35 million people worldwide suffer from itand that the number of sick people could reach the 115 million people in 30 years. In our country, the association France-Alzheimer considers that a quarter of people over 65 will be diagnosed with Alzheimer's disease by 2020. Although, in some rare cases, Alzheimer's disease may be due to a genetic problem, the major risk factor is ageing. It is therefore logical that the prevalence of these diseases is correlated with increased life expectancy. But recent work also suggests that Alzheimer's disease could, under certain conditions, be transmitted between individuals. Its mechanism is reminiscent of that of prion diseases such as Creutzfeldt-Jakob disease, of which dozens of cases occurred following the mad cow crisis. Explanations.

Alzheimer's disease, a protein problem

Symptomatically, Alzheimer's disease manifests itself by a drastic deterioration of the psychic and physical faculties, due to the death of brain neurons. When the brains of patients who have died of the disease are analysed, two types of protein deposits are present.

Proteins are large molecules made up of a chain of smaller molecules, the amino acids. They are essential components of life: the cells and tissues of living beings contain thousands of proteins, whose functions are varied and specific (hormones, enzymes, structural proteins such as collagen, tubulin, which forms the "skeleton" of cells and gives them their shape, etc.). In Alzheimer's disease, some of these proteins become abnormal and accumulate.

The first type of protein deposits found in the brains of patients with the disease contains a protein called "Tau protein" (from the English word "tau"). Tubulin-associated unit). Normally, one of its functions is to stabilize the structure of neurons. In Alzheimer's disease, Tau is altered and no longer plays its role. Neurons degenerate, while abnormal proteins aggregate together and accumulate in nerve cells.

The second type of deposit is formed by the beta-amyloid peptide or Aβ (peptides are strings of amino acids, like proteins, but much shorter). The Aβ peptide comes from the cleavage of a large protein called APP. Located on the surface of neurons, APP is involved in their growth, survival and repair.

Normally, Aβ peptides are eliminated, but in Alzheimer's disease, they accumulate outside the nerve cells in the form of amyloid plaques, also sometimes called senile plaques. These deposits are also found around the blood capillaries of the brain and in the brain. can cause cerebral microhemorrhages. called cerebral amyloid angiopathies.

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Formation of amyloid plaques. Wikimedia

Proteins capable of contaminating others

The most remarkable point about the mechanisms causing Alzheimer's disease is that neurodegeneration does not result from a simple passive accumulation of proteins.

In fact, the proteins involved in Alzheimer's disease change shape, which alters their action at the cellular level. It is important to note that the role of a protein generally depends on its shape (which itself depends largely on the sequence of amino acids that make it up). It is this change in morphology that gives the Aβ peptide properties that are totally different from those of its normal form. Having become capable of self-aggregation, it can form deposits of amyloid fibres which are probably responsible for the death of neurons.

But that's not all: researchers have shown that toxic forms are capable of forcing their normal alter-egos to imitate them, and to adopt a pathogenic form as well! This phenomenon, known as "self-replication", explains how a diseased cell producing the toxic form of the peptide can "contaminate" the neighbouring cell.

This contagion from person to person also explains why, during the progression of Alzheimer's disease, the spread of brain lesions gradually spreads to the entire brain following a well-defined pattern in all patients.

What is Alzheimer's disease?

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Mechanisms reminiscent of prion mechanisms

This self-replicative process is reminiscent of what is observed in another neurodegenerative disease, the Creutzfeldt-Jakob disease. The latter is due to the propagation within the brain of a very particular pathogen: the prion.

Neither bacteria, parasite, virus nor fungus, the prion is nevertheless transmissible. The discovery of these "infectious protein particles" (the acronym prion is derived from the English proteinacious infectious particle) has been the subject of much ink and forced researchers to forge a new concept, that of "unconventional transmissible agents". Unlike other pathogens, prions have no genome (they have no DNA or RNA) and are composed exclusively of a single protein.

As with the proteins involved in Alzheimer's disease, cells naturally produce a "normal" version of the prion. It performs many biological functions, but its various roles are still poorly understood. It also has the property of folding and aggregating to form infectious particles. In their infectious form, prions are capable of infecting a new individual after ingestion of certain contaminated tissues, or via blood for example.

The great resistance of prions to conventional destruction processes has been at the origin of several major economic and health crises, such as the mad cow crisis in the 1980s and 1990s or the tainted growth hormone scandal.

Is Alzheimer's disease contagious?

The aggregation processes of the Aβ peptide and the Tau protein show similarities with that observed in prions. Is it possible, then, that Alzheimer's disease can be transmitted between individuals by the same mechanism as the prion? Various groups of scientists have sought to answer this question.

Experimentally, several research teams have been able to induce the proliferation of peptide aggregates Aβ in animals from laboratory. In addition, more recently, various studies have suggested the existence of transmission case iatrogen of the pathogenic Aβ peptideresulting in cerebral amyloid angiopathy. Growth hormones produced before 1977, in particular, would not only have been contaminated by the prion, but also by the peptide Aβ, and could have been involved in the development of Alzheimer's disease.

In parallel with the publication of this work, another so-called "at-risk" population has been particularly detailed, that of patients who have received a dura mater transplant. This thin fibrous membrane that protects the brain could be removed from cadavers to serve as a "dressing" following invasive neurosurgical operations. This practice has been banned in France in 1994because dura mater grafts have been responsible for the iatrogenic transmission of the human prion.

Three studies (Swiss, Japanese and international) have respectively shown that 71.4 % 81 % and 61.5 % Patients who have received this type of transplant have subsequently developed cerebral amyloid angiopathies. Although formal proof of graft contamination cannot be provided, the location of the lesions and protein deposits strongly suggest that the graft was responsible for the change in shape and aggregation of the recipient's Aβ peptides.

One study also suggested that surgical instruments used in neurosurgery may also sometimes be a contaminant sourcealthough the risk is probably very limited. Nevertheless, the authors of this work suggest toimprove sterilization procedures.

Is Alzheimer's disease a prion disease?

From a mechanistic point of view, it is clear that Alzheimer's disease is similar to prion diseases. If one confines oneself to the strict definition of the word prion, an infectious protein particle, then Alzheimer's disease should be included, since the transmissible nature of the toxic protein assemblies that cause it has been demonstrated, at least experimentally.

However, as research results have emerged, the concept of the prion has broadened: the existence of different prion strains was revealed, as was its ability to "mutate" and adapt to its new host. In this respect, prion diseases are different from Alzheimer's disease. In the current state of knowledge, it would therefore seem more accurate to describe the latter as a "prion type disease" or "infectious amyloid". Or to extend the term "unconventional transmissible agent" to the protein assemblages responsible for Alzheimer's disease.

Angelique Igel-Egalon...Research Engineer, Inra

This article is republished from The Conversation under a Creative Commons license. Read theoriginal paper.

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