HSV-1 hypothesis: a personal experiment

Testing the HSV1 Hypothesis

Dangerous Speculation and Experimentation

by CrashTestDummy

WORK IN PROGRESS, NOT FINISHED YET, HOPEFULLY BY THE END OF MARCH 2014

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* Alzheimer's Disease may be caused by Herpes Simplex Virus Type 1.  
* Amyloid Beta 42 Aβ42 may be the brain's immune response to HSV1.
* APOE4/4s seem unable to process insoluble Aβ42 to soluble Aβ40.
* Aβ42 collects as solid plaques, the post-mortem physical evidence of A.D.
* More than 20 trials attempting to eliminate Aβ failed, some causing fatal brain infections.
* Lifelong treatment with Valacyclovir may suppress HSV1 and reduce Aβ42 production
* Eliminating existing Aβ42 plaques will be very difficult without compromising immunity
* I shall design a measurement and treatment protocol, and start testing myself.
* Though I hope to collect data that will help younger people, this may not help me much, and it may kill me.
* DO NOT TRY THIS YOURSELF

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The following wiki page is the background and and rationale for a personal experiment. Unless something stops me from adding to this page, I would prefer you to make your comments on the discussion page, and I will change this page myself to accomodate them.

Perhaps 50% of what follows is baloney - but I don't yet know which. I hope to improve it over time, but if something happens to me, I want to share my explorations and suppositions now, so others can avoid my mistakes. I will add more citations in time.

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The Evolution of the Human Brain

Like all brains, mammal brains grow a fixed number of neurons which last through life. Like all brains, most of mammal neurons have fixed wiring and functions and mostly can't repair damage. Vision, hearing, taste, smell, movement, etc. are directly connected to structures differing little from reptiles, fish, and other simpler animals.

Mammals have a unique structure, the cortex, which seems to have evolved from the olfactory bulbs of mouse-like ancestors. These warm-blooded small animals may have lived underground and oriented themselves by smell - remembering many "smell trails" and learning to abandon old food sources and find new ones required more flexible memory than reacting to fixed cues and habituating to a small range of stimuli. Therapsid dinosaurs, of whom birds are the surviving remnants, shared some of this flexibility, but evolved in a different direction.

Primates, and especially our near-kin chimps and bonobos, have enormous cortexes compared to all other primates, and human cortexes are three times larger than chimp cortexes. Size is not the only measure - human cortexes have more layers of connectivity and more crossbrain connectivity than other primates, and far more than non-primate mammals.

Cortex neurons grow "long" axons (outbound signals), dendrites (inbound signals), and create and destroy synapses between them. The synapses are nanometer-scale structure whose connectivity changes with contact area and spacing, with kinase molecules cutting protein scaffolding to rapidly (seconds?) change their shapes and the strength of the signals they pass. Signalling is chemical, not electrical; that makes the brain much slower than wires in a computer, and it also makes experimental electrical interconnect very difficult.

Many brain researchers accept Eric Kandel's epigenetic DNA model of memory, which describes how habituation (selection between behaviors) occurs in very simple, easy-to-study animals like Aplysia sea snails. In principle, an Aplysia can lose a neuron and regrow another that does the same thing, because the repertoire of possible behaviors is determined by DNA only.

But Kandel's model is a poor fit for humans. Mammals learn and must create their repertoire de novo by creating new structures, so when the structures go away, they take their memories with them. Fortunately, the memories themselves are encoded in redundant networks of neurons, and brains extrapolate (confabulate?) around missing neurons, modifying but not completely losing memory.

The amygdala and the hippocampus (near the center of the brain) signal the cortex to remember the patterns it is currently running, in association with other patterns of memory. Our brains remember sequences and rhythms, patterns and associations, not facts per se. Human cogitation is an epiphenomena on rich and interconnected patterns, and the system is continues to survive in spite of serious damage. The sense of identity also survives and adapts, but that identity may be objectively quite different over time. An Alzheimer's patient with advanced memory loss still thinks of themselves as a person - even after they can't remember their name.

So structure is critically important to human brains, not just the general instructions stored in our DNA. We can't regrow neurons - we die with the cells we developed with (or fewer). Even if new neurons could be added in place of missing ones, they cannot connect the way the old neurons did, that information is lost.

To bacteria, humans are huge sacks of nutrients, and without aggressive immune systems, we would soon become microbe chow. We have many forms of immune systems, macrophages (white blood cells) and antibodies in the blood, superoxides and other bacterial poisons, and no doubt other systems we don't understand yet. These systems classify every protein as friend or foe, with a very narrow definition of "friend".

Complicated, variable human neurons and synapses are too variable to meet this narrow definition, so the brain is walled off from the rest of the body with multiple membranes that compose the blood-brain barrier. This keeps out many pathogens, but it also excludes an immune system that could misidentify axons and synapses as "foe" and damage them. It does not take much to damage a synapse.

But the brain is still tasty, so it must have its own defenses and immune system. Since it lives inside a bone box, and is as fragile as pudding, these defenses are poorly understood; one (of many) plausible systems involves amyloid beta proteins, and will be discussed in the next section.

Humans are social creatures; we evolved to live and work and create children in groups. So individual immune systems protect more than an individual, but prevent the spread of infection to the entire group. If a human incubates a disease in some small portion of their body, it is better to destroy that portion than to risk death for the whole body. If necessary, it is better to destroy the whole body than a closely related kin group which could easily pick up the infection that body is incubating. So there is a strong bias for a hypersensitive, berserker immune system, and few plausible reasons to restrain that immune system in an older adult whose children are old enough to survive on their own.

Memory is one reason - an older human may have skills, relationships, and environmental knowledge that can help a whole clan survive. After this knowledge is passed on to many younger members of the clan, those memories are less indispensable. At some age, incubation overrides indispensability, and we can expect the immune system to be tuned to that. We can also expect the immune system to be tuned to the evolutionary past, so ours may be optimized for five thousand years ago, not the circumstances of 21st century civilization, with more crowding and interaction, and an evolving externally managed immune system.

The bottom line:

* Our brains have their own immune systems
* Immune systems are aggressive and protect the clan at all costs (including the individual)
* Nanometer structure is critical to individual survival
* New connections may be made, but damaged connections do not grow back

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Herpes Simplex and Amyloid Beta

MORE LATER

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Diet, Exercise, Infection Suppression and Amyloid Flow

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The Failure of Anti-Amyloid Therapy

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The Manchester HSV1 Model

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Self-Experimentation With Valacyclovir

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Long Term Survival

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