The pathological version of tau that destroys neurons in Alzheimer’s would be an attempt to respond to infections: it once protected us.
The chemical reaction that gives rise to neurofibrillary tangles, the clusters of tau protein lethal to the neurons typical of Alzheimer’s, may have been, in a very distant time, protective for the brain. A study published in Nature Neuroscience reinforces the idea that a mechanism that today causes neurodegradation – the so-called hyper-phosphorylation of tau protein – is the consequence of an antiviral response, the attempt to defend the brain from an infection.
Why does Alzheimer’s exist today?
Scientists at Mass General Brigham, a research institute affiliated with Harvard Medical School in Boston, started from a question: why – they asked themselves – has our species evolved genetic mutations that predispose to Alzheimer’s, which are highly widespread today, if they are so little advantageous? The new work suggests, as already hypothesized in past studies, that processes that today are pathological may once have had a protective role.
Genes that predispose to Alzheimer’s may have constituted an evolutionary advantage against infections when we lived for thirty years at most, while now that we have reached such an extended lifespan, they may increase susceptibility to this form of dementia.
Alzheimer’s: how tau degenerates
Tau is a protein expressed in abundance by neurons that serves to stabilize microtubules, the protein filaments that form the cytoskeleton (the internal scaffolding of cells) and that allow nutrients and other molecules to be transported into cells.
In the case of Alzheimer’s, the tau protein acquires too many phosphate groups, chemical packages that can modify the activity of enzymes: that is, it becomes hyper-phosphorylated – to put it very simply, it modifies excessively, forming tangles within neurons which degrade their structure and compromise the transport of signals.
The meeting between tau and the herpes virus
The authors of the study made cell cultures of human neurons prone to producing hyper-phosphorylated tau “meet” with the herpes simplex virus 1 (HSV-1: the one that usually causes infections on the lips), already linked to Alzheimer’s in the past.
The infection of the neurons caused the hyper-phosphorylation of tau which, therefore, formed the typical tangles, in a pathological mechanism very similar to that of Alzheimer’s. Tau has been shown to bind to the capsid of the virus and neutralize the infection, effectively protecting neurons and preventing the virus from attacking cells.
“Our findings reveal an important new role for the tau protein as an antiviral protein against HSV-1 and probably other viruses,” explains William Eimer, researcher at the Department of Neurology at Massachusetts General Brigham and first author of the study.
“The tangles may have originally formed (…) to prevent the spread of the virus from one neuron to another in the brain.”
