Alzheimer's disease affects close to 36 million people worldwide. The disease is heterogenous, showing a range of origins, clinical courses and lesion profiles. Today still, the factors affecting its clinical course remain poorly understood.

A hallmark of Alzheimer's disease is the presence of amyloid-β (Aβ) protein deposits in the brain. These deposits set off a cascade of events that leads to synapse loss (thus limiting inter-neuron communication) and ultimately to failing memory and impeded daily function. Several studies have established that the intracerebral administration of Aβ-contaminated compounds can induce Aβ pathologies.

Some people have genetic mutations that can induce the production of mutated forms of Aβ. In their recent work performed in a murine amyloid pathology model, the LMN's MIINDt team (MIRCen) showed that a single exposure to certain forms of mutated Aβ can aggravate Alzheimer's disease lesions and other downstream aspects, notably as concerns cognition, functional connectivity and synaptic density, several months after the inoculation event. Moreover, the mutated Aβ appears to increase native Aβ aggregation. Obviously, the inoculation of mutated Aβ into the brain lacks clinical pertinence. However, the study does demonstrate how a single event regulating Aβ aggregation and synaptic health can have long-term impact, and furthermore has the originality of demonstrating behavioral effects.

This first study shows that a single sporadic event like mutated Aβ inoculation can aggravate the evolution of Alzheimer's disease and affect the clinical course months after the event itself. Its importance resides in its suggestion that Aβ is able to initiate mechanisms regulating a cascade of events over a long period. Further studies are now needed to determine the relationships between mutated Aβ and its functional effects.

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