In Simple Terms: Alzheimer’s Disease

Alzheimer’s Disease occurs when there is an increase in neuronal cell death in the hippocampus. The hippocampus is the part of the brain that is involved in learning, memory, as well as with emotional responses. If you are going to lose neurons in this part of the brain, this will obviously have an effect on your learning and memory. Brain imaging from Alzheimer’s patients shows atrophy (or degeneration) of the brain in areas that are involved in learning and memory.

Risk factors of Alzheimer’s include:

1. Age- risk increases after the age of 6o and doubles every decade after that

2. Genetics- if your relative has the disease, your chances of having it increase

3. Cholesterol-high levels of cholesterol are related to an increased risk

4. Injury- a head injury will likely increase the risk

5. Gender- this disease is more common in females than in males

6. Lack of mental stimulation

The critical and toxic molecule in Alzheimer’s disease patients is beta-amyloid, a protein that forms plaques in the brain. Beta-amyloid is formed when an Amyloid Precursor Protein (APP) is cleaved into Ab-40 and Ab-42 (both beta-amyloids) by an enzyme called gamma-secretase. Of the two, Ab-42 is the toxic substance that forms plaques in the brain. An increase in Ab-42 causes degeneration of neurons in the brain. Drugs that inhibit gamma-secretase activity have been found to be effective in reducing the progression of Alzheimer’s.

The mechanism by which beta-amyloid induces death of neurons is through its interference with the reuptake of glutamate. Glutamate binds to the NMDA receptor in the brain, which in turn lets calcium ions flow into the channel. However, if too much calcium comes in, it induces activation of calcium-activated proteases, which leads to cell death. Drugs that inhibit NMDA activity (like Memantine) are also used as treatment for Alzheimer’s.

DNA damage within neuronal cells is also prevalent during the course of the disease.
Even though the Alzheimer’s brain increases DNA repair enzymes as well as BCL-2 ( a component that protects against cell death), the battle between damage and repair is ultimately won by the degenerative neuronal cells. Thus, there is more damage than repair occurring in the brain of these patients.

Here’s what YOU can do to slow this degenerative process:

1. Crossword puzzles. Sudoku. Anything that keeps your mind alive.

Learning and mental stimulation enhances BDNF (brain derived neurotrophic factor), a neurotrophin that supports the cells and makes them ‘feel better’.

2. Take a hike.

Physical activity increases BDNF.

3. Eat healthy

Diets high in fats and sugars decrease BDNF activity.

4. SLEEP

Sleep enhances the activity of BDNF.

5. Quit stressing

6. Get your Vitamin E

Vitamin E slows the progression of Alzheimer’s.

Other interesting facts:

-Patients with rheumatoid arthritis that take Ibuprofen do not get Alzheimer’s because Ibuprofen affects the activity of gamma-secretase in such a way that it reduces the production of beta-amyloid.

-Bilinugals have a lower chance of getting Alzheimer’s

Reference Websites:
http://www.cmj.org/Periodical/paperlist.asp?id=LW7347&linkintype=pubmed
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772133/?tool=pmcentrez

*Lecture at University of California, Irvine