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by tyu100 2895 days ago
No. The beta amyloid protein is the primary 'cause' of Alzheimer's. It builds up in the brain and kills neurons and synapses. Tens of billions of dollars have been spent developing drugs to reduce the amount of amyloid in the brain to try and combat Alzheimer's, none of which has led to an effective treatment.

This newer theory is that the cause of the amyloid build-up is an immune response to the herpes virus increasingly infiltrating the brain (as you get older the blood/brain barrier that protects your brain from infections weakens) so a possible treatment is to try and reduce the levels of herpes infection rather than attacking the amyloid protein which is your body's immune response to the herpes infection.

The APOE4 gene is infamous for increasing amyloid production and being a major risk factor for early-onset Alzheimers and so carriers of the gene are often used in studies to see the effect of treatments. (@subcosmos below has a good explanation of what this gene actually does)

3 comments

The thing about viral infections of the nervous system is that you don't even need to consider the blood brain barrier. Viruses travel backwards through neurons by hijacking microtubule transport networks, and many groups have hypothesized in the literature that it could be getting into the brain by simply infecting a peripheral nerve and traveling up the spinal chord.
> Viruses travel backwards through neurons by hijacking microtubule transport networks,

How does this help crossing the BBB? Can you give a citation?

Check out Figure 1 in this paper. The model effectively is that HSV infects a great many people in early life, and becomes latent in neurons until old age. Then it suddenly wakes up again and travels to the brain. All it takes is an infected muscle or other tissue, allowing the virus to get into the nerve. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546524/

Some VERY notable statistics mentioned in the paper : "Such studies have revealed endemic infection rates of 31% in children aged 6–14, rising to 49% in adults aged 14–49, and to a high of 80–90% in the population over 65. In one study of 40 autopsied TGs, HSV-1 sequences were amplified from DNA or RNA extracted from 81% of TGs from demented subjects, and 74% of controls"

I blogged about these connections here, for I think that this retrograde transport phenomenon might explain Tau phosphorylation, which is a secondary hallmark of Alzheimer's and other dementias : https://medium.com/@InfinoMe/cholesterol-have-we-shot-the-me...

Nothing about the BBB in that paper.
As its name implies, the blood brain barrier protects the brain from whatever happens to flow in the blood stream. The herpes virus enters the brain by another channel : the peripheral, somatosensory nerve cells whose axon has a T shape. One prong of the top bar goes to the peripheral tissue, and the other prong goes up to the brainstem.
thanks for the explanation! That wasn't clear to someone who has enough biochemistry and biology to be dangerous but with no experience in physiology.
Why swim (cross BBB) if you can take the bridge (infect neurons)?
We don't know that beta amyloid causes Alzheimer's. (I was a grad student in a lab that did research on beta amyloid)
>The beta amyloid protein is the primary 'cause' of Alzheimer's.

I think this is still an open question. Beta amyloid proteins may not be the root/fundamental cause.