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Friday, February 10, 2012

The GUIDE: Treating Alzheimer's Disease [Full link to blog for email clients.][FT:C44]

The plain truth of the matter is that there is no cure for Alzheimer's Disease (AD).  If neurons in the brain could be grown and replaced like skin, muscle or liver cells,  then it might be possible to regrow the lost brain cells, but unfortunately, just replacing cells is not enough - our memory, everything we have learned, and even our very personality is a product of the connections between neurons that have built up over a lifetime.

Image Copyright Alila Sao Mai, 2012
Used under license from
What we can do is to support the functions of the undamaged neurons while the symptoms of AD are still mild.  In the previous blog is was mentioned that neurons using acetylcholine (ACh) seems to be preferentially affected by AD.  Whether the disease specifically targets these neurons or they simply happen to be prevalent in the first brain areas affect is immaterial.  What happens is that as acetylcholine neurons die, the amount of signal they can represent is decreased, somewhat like listening to a music player radio with dying batteries.  The brain is highly redundant, and most neural signals are carried by multiple neurons.  Thus if we could find a way to boost the signal of the remaining neurons, we might be able to delay the debilitating phase(s) of AD. 

In the diagram at right, I show a typical "synapse" between neurons.  At the top is the "presynaptic neuron" which is the one sending the signal.  At the bottom is a portion of the "post synaptic" neuron which receives the signal. Signals in the brain are represented as the distribution of electrical energy - similar, but not exactly like the digital "bits" of a computer.  However, in order to cross the gap between neurons, that electrical signal is converted to a chemical one.  The positive electrical potential that results from activity in the presynaptic neurons causes release of a stored chemical - the neurotransmitter.  The neurotransmitter diffuses into the space between neurons, and when it encounters the neurotransmitter receptors on the postynaptic neurons, it causes the protein to change shape, quite frequently opening a channel that allows positively charged molecules into the neuron.  Accumulating positive charge starts the entire process of electrical activation again in the new neuron and the process repeats with transfer of signal from neuron-to-neuron. 

The neurotransmitters are short lived - there are enzymes which break them apart, as well as means for the presynaptic cell to reabsorb the components.  The reason is that neuron-to-neuron signals should be short, otherwise the information will get lost in continuous signal.  But, if the signal is getting weaker due to AD, it makes sense to boost it by prolonging the action at the postsynaptic neuron.

There are a few classes of drugs that can perform that action - the most prevalent drugs - donepizil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne) all work by stopping or slowing down the breakdown of ACh.  They are useful to "boost the signal" that naturally occurs by prolonging the activation of the postsynaptic neuron.  A second method would be to raise the background activity at ACh receptors by supplying a small amount of an ACh-like drug so that the ACh released by neurons would be more effective in activating the post-synaptic neurons.  While much work is ongoing in this field, no drugs of this type are currently in any but experimental use. A third method is to reduce some of the other, "competing"  activity in the brain, particularly in areas in which there are many ACh and glutamate neurons.  Mematine (Namenda) blocks one type of glutamate receptor, thus producing a "quieter environment" for the ACh neurons.  As a last resort, once AD patients start to show symptoms of personality disporders, aggressiveness, hallucination, etc., those symptoms can be treated with antipsychotic drugs.

It should be noted that all of these treatments are symptomatic ones, and they nothing can "cure" or reverse AD.  However, there is hope in that supporting memory, decision-making and other activities of the brain can slow the progress of the disease and postpone the onset of more symptoms.  There is an old saw about "use it or lose it" and it appears to be true - using the brain strengthens the synapses between neurons.  Strong synapses deteriorate slower, and while starting Aricept or other treatment after the onset of AD won't bring back lost function, it will help to maintain what remains.

By the way, vitamins and gingko biloba have no effect on the onset or progress of Alzheimer's disease, no matter what any source may say.  No effect means no effect.  Obviously a good diet is important, and omega-3 fatty acids and antioxidants are important to normal brain health, so certainly include them (within reason) in your daily intake.

Ideally, as stated above, we should find a way to replace the neurons, remove the amyloid plaques, or fix the neurofibillary tangles.  In fact, there are stem cell therapies designed to supply the glial cells that normally support the active neurons.  Replacement of neurons may have some benefit, but as stated above, they would need to be "taught" with all of the experience of a lifetime.

Perhaps what is really needed is a science fiction nanomachine that can selectively break up beta-amyloid and fix neurofibrillary tangles.  Then we could move on to more nanomachines that rebuild the lost synapses and restore memory from a previous template.

Hmmm.  Where have I heard that before?

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