As already mentioned in the previous post, beta amyloid protein is the main component of senile plaques, while tau protein is the main component of neurofibrillary tangles. The appearance of the first and second indicates a pathological change in the brain. Both were described by Dr. Alzheimer in his patient Augusta Deter.

Post information is based on data from the course «Understanding Alzheimer's Disease: Molecular and Genetic Approaches».

My previous post on how Alzheimer’s desease was discovered you can read here.

Neurofibrillary tangles consist of tau protein, which during normal functioning promotes microtubule polymerization and controls other cell actions, but in pathology it is deposited into fibers measuring 20 nm. The tagles are closely related to the death of neurons in case of the disease. The accumulation and death of cells does not occur in one day, this process can last for a couple of decades. And because tau protein is so strong and resistant it can be found in the extra cellar area after a cell’s death.

Some scientists consider that tau protein plays a critical role in the causes of the disease as it is directly connected with neurons which are under risk. Moreover, it is essential in stabilizing microtubes which maintain dendrites and axons in a right place.

EXPERIMENTS

There were several experiments done which revealed some important conclusions.

It was paid attention that tau protein passes a few stages of polymerization (oligomerization), so this means that tau can spread in the brain distributing Alzheimer’s disease to more quantity of cells.
The first experiment involved Methylene Blue to effect tau protein polymerization. It did not show positive results. The second one was done with lithium which could influence kianese regulating tau phosphorylation. By the way, lithium is used as a psychotropic element in bipolar disorders, but in case of tau protein it did not help.

Screenshot from the course

PHOSPHORYLATION

I would like to stop at such pathologic issue of the diseas as phosphorylation. When scientists did researches about tau rotein in the 80-s, they defined that neurofibrillary tangles were extremely phosphorylated which signifies that tau protein have a lot of phosphates attached to serine and theonine amino acid residues. The thing is that tau protein controls microtubes stabilization, but once it is phosphorylated it cannot perform this function any longer. In this case microtubes disassembly.

If to consider the disease’s pathology and what its function is in the exposition of the illness, here should be lined 3 presupposition ideas:

1. If to break transformation on early stage the desease could be extinguished because they set up the environment to cause the disease (causative).
2. Amyloid and tau are in fact «observers» and just wall off the proteins (irrelevant).
3. Both amyloid and tau signify major response to the disease, meaning that they are the central point. At the same time being central issue does not refer to beginning of the disease, that is why occuring in normal aging they do not cause a problem.

Here is a list of some observations on tau protein made:

• Amyloid deposition in the brain testify lowering of oxidative stress.
• Oxidative process is a usual procedure in the body and to prevent its negative effect the body possesses incredible mechanisms: modified enzymes, chelators tying up metals.
  Such oxidative stress reduction conditioned by amyloid was discovered in Down syndrome and Diffuse Lewy Body disease as well.
• Amyloid stabilizes copper which causes oxidation.

Relying on the above said maybe amyloid precursor protein mutaions along with presenilin 1 and presenilin 2 can be causative and be a reaction to bring the brain to normal state. Consequently, if to eliminate them, this could lead to a damaging effect rather than to a positive one.

It is undestandable that people having genetic mutations are outside of biology, they possess defects. In most cases the disease has the following develompent: pathologic processes start after the age of 40 with formation of neurofibrillary tangles, and after the age of 60 the affected cells are ruined.

Scientists continue to study the Alzheimer's disease with all their attentiveness and desire to find the key of the problem.

Be healthy!

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