Causes of Alzheimer’s Disease

The causes of Alzheimer’s disease are still in question, and the changes that take place in the brain are constantly being studied.  There are several theories about the causes underlying Alzheimer’s disease including:

1. The brain doesn’t make enough acetylcholine, a neurotransmitter.

2. Beta amyloid, shortened forms of a protein, join together to form plaques in the brain.

3. Myelin, an insulating material that surrounds neurons, breaks down.

4. Tau tangles form in the brain.

Let’s discuss that last theory, the tau theory, in more depth.  The tau protein interacts with and stabilizes microtubules, the scaffolding structure of cells.  It is found mostly in neurons.  Two different changes in the tau protein can affect its ability to function normally – isoforms and phosphorylation.

Different isoforms of the tau protein can be present in cells.  Isoforms of tau are different versions of the protein.  They are made when the gene from which the protein is created is cut in various places creating different sequences.  These isoforms have variable structures with different attributes.  Some of the isoforms of tau are more likely to form tangles than others.

The tau protein can also be changed after the protein is made through a process called phosphorylation.  Phosphorylation adds a phosphate group to the tau protein.  If several phosphate groups are added to the protein, tau can self-assemble into the tangles that are characteristic of Alzheimer’s patients.

Tau protein aggregates into filaments (left).  The filaments form tau tangles (right).

Tau tangles can lead to disintegration of microtubules in neurons.  This can then result in malfunctions in the communication between neurons leading to cell death and cognitive impairment seen in Alzheimer’s patients.