Alzheimer’s Heritability, Selection, and Affects of Inbreeding

Heritability


The role of heritability in Alzheimer’s disease is a question that is heavily contemplated and explored by researchers. A study published in the Archives of General Psychiatry worked to quantify the role that genetics played in the onset of the disease. Researchers from the University of Southern California looked at 392 sets of elderly twins over the age of 65. The use of twins allowed scientists to look at both environmental and genetic factors of the disease. In the case of identical (monozygotic) twins, all of their genes are shared, so if the disease is highly genetic than it should be observed in both or neither of the twins. If only one individual had it, it is likely to be more influenced by environmental factors. It was found that identical twins were more likely to both have the disease when compared to non-identical twins, which suggested that genetic factors are relatively significant. The estimated heritability was found to be between 58% and 79%. This study confirmed the Alzheimer’s appears to be heritable and that the genetic factors influence both male and female patients, but there are also some environmental factors that affect the development of the disease. However, what all of the environmental factors maybe are still not completely known.


Alzheimer's risk 'is 80% genetic'. BBC. news.bbc.co.uk/1/hi/health/4686806.stm.


Selection


The onset of Alzheimer’s typically occurs later in life, so it seems that selection would have very little to no effect since the phenotype is not exhibited until after the usual reproductive age. It also does not seem plausible that the history of Alzheimer’s in a person’s family history would limit their reproductive prospects either.


Inbreeding


In most cases, only dominate genes have been associated as a possible cause of Alzheimer’s disease. However a study published in Neurology exposed the idea that a recessive gene may play a role in the development of the disease. 821 elderly residents of an Arab community called Wadi Ara in Israel were screened for the disease. It was found that 20% of individuals over 65 had the disease and 60% of individuals over 85 did as well. This was compared to an overall 40% occurrence in the general population. The dominate gene (APOE-4) which is commonly linked with Alzheimer’s was found to be of low occurrence in this population (only 15%). However, the Wadi Ara community is known for its large family size and high frequency of inbreeding (about 44%), which leads researchers to look for a recessive gene that would be exposed by the inbreeding of the population.


This is not an isolated case. Other populations, such as the people of Sangueany in Canada also have a reasonably high rate of intermarriage and a higher occurrence of Alzheimer’s disease. Unfortunately, Americans often refuse to participate in such studies, up to 30%, which limits the research that can be done in the United States regarding the connection between Alzheimer’s and a possibly dangerous recessive allele.


Buckles, Julie. First evidence recessive gene plays role in Alzheimer’s disease. Genome News Network. 2000.
genomenewsnetwork.org/articles/09_00/Alzheimer_recessive.shtml.

Why Should Doctors Know About Evolution??


d To understand the relevance of laboratory studies on animals and how it relates to advancements in human health care:

• With no understanding of evolution, it would be unclear how laboratory studies on animals correlate with humans. A working knowledge of evolution, however, articulates that all organisms have a single common ancestor. Animals, themselves, have a closer, single common ancestor and share the same genes from this ancestor. This orthology gives an explanation as to why studies on animals relate to humans: all animals have the same general body components, functions, processes, reactions, and development. From this it can be assumed that the results of studies on animals will be similar if applied to humans.

d To be able to continue to provide effective health care:

• Rapidly mutating viruses, such as HIV and influenza, are major health concerns and should be fully understood by doctors. Pathogens reproduce quickly and have a high mutation rate, causing them to be able to evolve more quickly than the host population. Human immune systems, as well as the medicines we are prescribed, select for pathogens that can evade our immune systems if we are reinfected. The more successful genotype then becomes more common, and is therefore resistant to treatment. Doctors must understand how pathogens may evolve, and also be up to date on the current forms of pathogens such as influenza, in order to maintain the effectiveness of treatments and vaccines in the face of the evolving pathogen populations.

d To understand the condition of the human population

• The environment in which humans live has evolved much more rapidly than the human population itself. Therefore, it can be speculated that humans are not truly adapted to their current environment. This may be one reason that some of the diseases (such as breast cancer) afflicting humans exist. The lack of adaptation may also explain some human behaviors such as parental care.

d Understanding natural immunity/ repair mechanisms

• The cells in the human body can evolve and change. The cells with better fitness are more likely to survive and therefore may allow the body to rid itself of a fatal genetic disease ( such as adenosine deaminase deficiency).

Knowledge gained from the paper on FFI:

n Katie - I learned that protein misfolding can cause a myriad of different problems/diseases, and that small changes can result in similar diseases. I had never heard of FFI before reading this paper, and was surprised to learn how similar it is Alzheimer's disease. Studying protein misfolding will help to better understand the effects resulting from different protein folding arrangements. This knowledge can then be used, at least theoretically, to help find cures for the resulting diseases. The similarity of some of the diseases may allow a chain reaction to be put into motion with one new cure/find being able to cure multiple diseases with little or no change in the formula.

n Megan - I also have never heard of FFI before now, and I looked into it a bit more. According to Merck Manuals, it occurs in the PrPc protein and another form occurs without the mutation, it is called sporadic fatal insomnia. I think that identifying diseases such as this (both symptoms and causes) may help find cures for existing diseases (such as FFI and Alzheimer's) while also explaining other symptoms and problems that people experience with no explanation for them. It seems as if there are not many families that have the mutation, but it raises the question if there may be more, or simmilar mutations that have other symptoms.

n Hailey - After reading about FFI I felt that protein folding and dementia diseases made more sense to me. I learned about a disease that is much more understood than Alzheimer's but very similar as well. This really clarified and reaffirmed the concept of protein folding and misfolding for me by presenting an interesting example.