Age-Related Macular Degeneration & Alzheimer’s

Similar Diseases, Different Locations, Possible Common Treatments

There are many similarities between two age-related diseases (Age-related Macular Degeneration and Alzheimer’s disease) that can affect thousands of people world-wide. In the United States there are 11 million people that have some form of AMD and it is estimated to grow to 22 million by the year 2050. Furthermore, in 2016 it was estimated that the cost to care for those with AMD was $512 billion. Worldwide it is estimated that by 2020, there will be 96 million people with AMD. National Eye Institute 

The second aging disorder that causes high degree of damage is Alzheimer’s disease. Presently, in the United States there are 5.4 million people with Alzheimer’s disease and this will increase to approximately 13.8 million by 2050. In 2016, the cost for caring for these patients was $236 billion. Worldwide the numbers of Alzheimer’s patients are estimated to be 44 million and the global cost is $605 billion. Alzheimer’s Association

Similar Risk Factors

The risk factors for both AMD and Alzheimer’s disease are very similar to each other. These include aging, smoking, and high cholesterol. Both diseases are found more frequently in women than men and in approximately 5% to 15% the diseases are found in more than one family member. There is also a genetic risk factor of a lipid transport protein called Apolipoprotein E (ApoE) that provides elevated risk in AMD patients if they carry the allele 2 variant and higher risk in Alzheimer’s patients if they carry the allele 4 variant.

In AMD and Alzheimer’s disease there are 3 events that make the pathologies very similar except that they are found in different locations, either the retina or the brain.

1. Amyloid beta is a protein that is not present in normal tissues but larger quantities accumulate in the brain for Alzheimer’s patients and are identified to be plaques by MRI scans. The presence of these plaques is defining (pathognomonic) for Alzheimer’s disease. In AMD patients amyloid-beta deposits are found to accumulate underneath the retina and form small clumps of protein-lipid materials called drusen. This is significant because the amyloid-beta is very toxic and harmful to the surrounding cells and when it is accumulating in tissues, it causes the cells to be damaged and loss their abilities to function.

2. A second feature of both AMD and Alzheimer’s disease is that there are high levels of tissue damage, loss of function and a lot of cell death in the retina and brain.

3. Finally, both diseases have damage to the mitochondria, which are small units within the cells that are critical to keeping the cells alive. The mitochondria are the “batteries” of the cell providing energy to keep the retina and brain cells functioning. Mitochondria are similar to the batteries in a flashlight. You can have a very expensive flashlight but if you do not have good batteries, the flashlight will not work. It is a similar situation to the cell. As long as the mitochondria are healthy and providing energy the cells can function. However, when the mitochondria start to die, then the cells will lose their functions and cell death will occur. This is true for all types of cells in the body, such as nerve cells, muscle cells, retinal cells, heart cells, etc. In other words, healthy mitochondria are critical to keep cell alive and functioning well.

Future Treatments

Using a novel in vitro model called cybrids (cytoplasmic hybrids), Dr. Cristina Kenney’s laboratory has shown that when mitochondria from patients with AMD are placed into specialized human retinal cells, the AMD mitochondria will cause the cells to die more rapidly than normal because they are so damaged. With this important discovery, the goal of the research group has been to identify drugs and proteins/peptides that can rescue the damage AMD mitochondria and protect the retinal cells. Their research is moving forward very quickly and testing drugs is the top priority for Dr. Kenney’s group. By rejuvenating the mitochondria from ‘old-damage’ to ‘new-healthy’ will prolong the health of the retinal cells and protect vision loss from AMD. What is learned in these studies will have long reaching applications to other aging-diseases such as Alzheimer’s and Parkinson’s diseases.

Creating Cybrids to Study Age-Related Diseases

DEF Research Director Dr. M. Cristina Kenney’s research has shown that the mitochondrial DNA from different ethnic/racial populations may play a key role in determining that population’s resistance or susceptibility to disease (see previous article on 11/12/15 – Mitochondria and Age-Related Macular Degeneration). In order to study these effects, Kenney has developed the cybrid model using mitochondria from subjects of different ethnic/racial groups (Figure 1). The comparison of an individual’s mitochondria with that from other ethnic/racial groups (African, European, Asian or Ashkenazi Jewish) allows us to determine if their mitochondria determine that population’s susceptibility or resistance to disease and to response to drugs.

cybrids to study age-related disease
Figure 1 – Cybrids are cell lines with identical nuclei but the mitochondrial DNA from individuals of different ethnic/racial groups.

Personalized cybrids
Kenney’s cybrids are made with mitochondria from the blood taken from individual living donors. Looked at individually they are all really “personalized cybrids” because each cybrid test system has the mitochondria from the original donor and reflects the responses of that donor.

Using Cybrids to Study Age-Related Diseases

How is Kenney using these personalized cybrids?
Kenney is partnering with Dr. Pinchas Cohen, dean of the University of Southern California, Leonard Davis School of Gerontology, to explore how novel, small proteins produced from mitochondria might be used to treat a variety of age-related diseases such as age-related macular degeneration, Alzheimer’s, Parkinson’s, stroke and cholesterol. Cohen’s laboratory has discovered and characterized many of these new, small proteins called “mitochondrial derived peptides” (MDPs). His work has shown that these MDPs can protect brain cells from damage and early death, such as occurs in Alzheimer’s disease. Cohen and Kenney are now testing these MDPs in the K and H cybrids to assess their protective effects to stop retinal cell death, such as seen in AMD.

Kenney explains her approach:
“Our cybrid system represents a very powerful technique. We are now using the Ashkenazi Jewish population as an excellent model to learn how the mitochondria, with their unique mtDNA, influence the risk factors for AMD. We plan to extend the study to investigate Ashkenazi Jewish people’s susceptibility to Alzheimer’s disease, heart disease and stroke. Eventually, we believe the findings for the K haplogroup mitochondrial DNA will be applicable to other groups, as well.”

11/17/15

Anthony B. Nesburn, MD  FACSAnthony B. Nesburn, MD, FASC
President/Medical Director
Discovery Eye Foundation