Studies published in leading scientific journals support the hypothesis of links between Alzheimer’s disease and exposure to herpes virus. Research work continues to confirm this scenario or not, knowing that Alzheimer is a complex pathology, most certainly determined by multiple risk factors.
Alzheimer’s disease is a neurodegenerative pathology that affects older subjects in its most common form. It is estimated that 1,200,000 people suffer from Alzheimer -type neurodegenerative diseases in France.
Discovered a century ago, this pathology remains very largely enigmatic and the exact mechanisms at the origin of its trigger and its poorly known evolution.
Among the hypotheses that are the subject of research, that of a link between Alzheimer’s and exposure to the herpes virus is reinforced by recent publications.
Brain lesions that cause a major cognitive disorder
Alzheimer’s disease is characterized by a set of microscopic lesions, initially confined in certain brain regions. The lesions then spread, over the evolution of the disease, in multiple areas of the brainbrain.
This slow and stereotypical progression of brain damage is accompanied by symptomssymptoms Graduated clinics (memory disorders, language disturbances, difficulty reasoning and planning actions, etc.). Alzheimer’s disease patients will thus develop a major neurocognitive disorder (the term of dementiadementia is sometimes used) leading to the loss ofautonomyautonomysocial isolation and the disappearance of the most complex, advanced and representative mental faculties of thespeciesspecies human.
The brain lesions which cause these dramatic clinical manifestations are schematically of two types:
- Certain lesions are present within neuronesneurones in the form of fibrillar tangles (we speak of “neurofibrillar degeneration”) made up of a proteinproteinthe tau proteintau proteinwhich accumulates in an abnormal form.
- Other lesions are identified in the extracellular space of the cerebral tissue, in the form of plates, whose chemical nature is mainly composed of a protein (the amyloid -ß or Aß peptide): the amyloid platesamyloid plates.
Understand Alzheimer’s disease in 2 minutes. © Brain Institute – Paris Brain Institute
Neurofibrillar degeneration and amyloid plates constitute the neuropathological signature of Alzheimer’s disease. However, other lesions are observed in patients’ brains.
To date, no preventive or curative treatment
Regarding the mechanisms at the origin of the disease, a significant advance occurred at the turn of the 90s with the identification, in certain patients, of mutations geneticsgenetics Involved in the production of the Aß peptide.
These discoveries have made it possible to sketch the hypothesis of the “amyloid waterfall” which proposes that the accumulation of aß peptide in the brain is a princeps and founder event which will cause all the other brain lesions and lead to dementia.
However, mutations responsible for an overproduction of Aß concern only a very low minority of patients (less than 1 %) and it is likely that a multitude of other causal factors are at work in the disease.
Without in -depth knowledge of the mechanisms responsible for Alzheimer’s disease, it is not illogical to note that today no preventive treatment or curativecurative Effective is not available, despite the very substantial therapeutic research effort.
The identification of causal determinants that cause Alzheimer’s disease and factors that modulate the risk of developing this disease or that modify the trajectory is a priority and mobilizes many research teams.
Possible links between Alzheimer’s and the herpes virus
Recently, a scientific article published in the prestigious review Neuron reported new data. This study analyzed two cohortscohorts of several thousand Finnish or English subjects and shown that a viral encephalitis (a inflammationinflammation From the brain following a viral infection) increased by 20 to 30 times the risk of later developing an Alzheimer’s disease.
These works followed other studies, in different countries, which indicated an increased risk of developing an Alzheimer’s disease after infection of the herpes virus (HSV-1), a virusvirus highly neurotropeneurotropethat is to say capable of entering the brain. These same studies underlined the protective effect (a reduction in the risk of Alzheimer’s disease) of an antiviral treatment.
More recently and even more convincingly of almost experimental studies in the human population have shown, in Wales, Australia and the USA, than the vaccinationvaccination against the Checkle-zona virusCheckle-zona virus (VZV), a virus from the same family as the herpes virus (HSV-1), significantly reduced the risk of developing dementia.
A hypothesis already defended 40 years ago
The hypothesis of a role of viruses, in particular herpes viruses, in Alzheimer’s disease is not new. She was defended over 40 years ago, by a neurologistneurologist Canadian, Melvyn Ball, who suggested that the reactivationsreactivations HSV-1 herpes virus (the famous fever button) could be accompanied by a neuroinvasion, that is to say penetration of the virus into the brain, and a degeneration of brain tissue triggering dementia of Alzheimer’s disease.
Research works later supported the hypothesis, by identifying “viral signatures” (corresponding to the proteins or genomegenome of the virus) which mark the presence of herpes virus (HSV-1) in the brains of patients with Alzheimer’s disease, especially in the amyloid plates.
These observations, as well as the first epidemiological studies, can however be criticized: highlighting an association between infection and Alzheimer’s disease is not enough to establish a causal link!
We could even apply, provocatively, that it is Alzheimer’s disease that makes the organism permissive to viral infections (and not the other way around!), Explaining the presence of viral material in the brains of Alzheimer’s patients.
Alzheimer’s and HSV-1: why research bounces today
The infectious hypothesis of Alzheimer’s disease has nevertheless been reinforced, more recently, by two series of experimental results:
- The discovery that the Aß peptide which precipitates at the heart of amyloid plates has antimicrobial functions and could thus participate in a physiological (immune) response in reaction to a viral infection,
- Succeeding in inducing, after infection by the herpes virus (HSV-1) in vitroin vitro (in cell cultures) or in vainin vain in animals, of an overproduction of peptidespeptides Aß and tau protein pathologicalpathological (The tau protein being, as we recall, the other molecular marker of Alzheimer’s disease).
The hypothesis of a scenario with several stages
Understanding the relationships between viral infections and Alzheimer’s disease has therefore progressed in recent years and new hypotheses emergingemerging.
Regarding HSV-1, the most studied virus, a scenario in several stages can be offered:
- Herpes virus infection (HSV-1) is common in our populations and the virus is able to enter into sleepsleep (phase de latencylatency) for several decades in some gangliaganglia nervous ;
- During aging the organism faces different stressstress which, combined with a drop in efficiency of the immune defenses of the elderly, will promote the release of latency from the virus and its propagation in the brain;
- The presence of active viruses in the brain will cause a local and tau local response, with low noise, in infected areas;
- These Aß and Tau lesions, associated with cerebral inflammation, will initiate a vicious self -employment circle leading to the intensification and propagation of lesions in other brain regions.
This hypothetical scenario will require an important effort of research to be validated (or deconstructs, thus goes science!). Experimental work is necessary in animals or on three -dimensional tissue preparations (brain organoids) to finely study the causal relationship between infection and biological markers of Alzheimer’s disease.
Studies continue
Epidemiological studies, in human populations, also continue and seek to refine the impact of levels of infection on the appearance or worsening of biomarkers of Alzheimer’s disease.
In the end, it is a set of disciplinary fields which is summoned and which requires the communication and sharing of knowledge and ideas between virologists, neurologists, epidemiologists, PathologistesPathologistesetc.
Confirm the role of viral agents in Alzheimer’s disease, but also in other neurodegenerative diseases (such as multiple sclerosis closely associated with the Epstein-Barr virus, still a herpes virus!) Would certainly open the porteporte to new preventive (vaccination) or curative (antiviralsantivirals).
It should nevertheless be kept in mind that Alzheimer’s disease is an extremely complex pathology and most certainly multiderminated by different elements or risk factors, genetic or environmental.
Concluding a unique cause of triggering the disease (like that of an earlier viral infection) is obviously an ineptus. It will be recalled in this regard that, although a large part (70-80 %) of the human population is infected with the herpes virus (HSV-1), this infection is not a condition sine qua non To develop the disease!
