Parkinson’s Disease And The Connection with Alzheimer’s

When I had interviewed with Matt Farrer in March my first impression was that he was just as impressive as his work. Dr. Farrer is a Parkinson’s disease researcher. In the last few weeks speaking with my colleagues I have heard them say exactly what I had gathered in my research before contacting him. His work has helped shape the entirety of Parkinson’s research.

If you were to perform an internet search on Parkinson’s disease research, the top results will consist of the Micheal J. Fox foundation and various Parkinson’s foundations. Matthew Farrer is on the board and funded by many of these organizations. His work identifying genes associated with Parkinson’s disease is a testament to his passion and dedication for research. Parkinson’s research is a puzzle of confusion and genetics.

Parkinson’s Disease: The Basics

Starting from the basics, the definition of Parkinson’s disease, according to Mayo Clinic (Which Matthew Farrer also worked for previously), is “a progressive nervous system disorder that affects movement.” Yet, what is the difference between Parkinson’s, Alzheimer’s, and just dementia? The answer to that question is unclear. Technically, Parkinson’s disease affects the parts of the brain associated with movement. Where as Alzheimer’s disease affects memory and is a common cause of dementia.Yet, people with Parkinson’s disease often times develop dementia and people with Alzheimer’s disease can have unclear symptoms. It is not uncommon for someone to have several diagnosis over short periods of time.

Unfortunately, although associated with advanced age, there are several types of early onset Parkinson’s(PD), and Alzheimer’s(AD). Early this week as I was conducting some preliminarily analyses on data. I noticed that the youngest age of all the patients was 46 years old. Speaking of statistics, just in the U.S alone  “Nearly one million will be living with Parkinson’s disease (PD) in the U.S. by 2020,”(Parkinson.org). Likewise, it is estimated that over 5 million people already have Alzheimer’s disease in the United States. Why do I keep mentioning both AD and PD together?  Because they are associated with one another not only symptomatic wise but genetically.

Connections

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The APOE gene, better known as, the gene that provides instruction for making the protein apolipoprotein E. . The protein is an important ingredient in lipoprotein. There are multiple alleles of this gene, e2,e3, and e4 being the major alleles. Most people have an e3 variant of this gene.Good news, there is no evidence that e3 is responsible for any diseases. Bad news, even just one copy of an e4 allele, can increase your chances of developing Alzheimer AND a type of dementia associated with Parkinson’s disease.  When I am developing a statistical summary table I always include APOE data if it is available. There are other genes associated with Parkinson’s as well.

The Puzzle

To begin there are two types of Parkinson’s disease, familial and non-familial. Familial with all dementia like diseases, is when there is at least 1 first relative, that has the disease, in addition to the patient. For those suffering from PD that do not have any known family members diagnosed with PD, they are labeled non-familial. 15% of people With Parkinson’s disease have the familial form of the disease. From those 15% there are two types of  inheritance: Autosomal Dominant and Autosomal Recessive. From basic biology, Autosomal Dominant  means that you only need one copy of the disease to be infected while Autosomal Recessive require both copies. For each type there are genes that have been found that cause such inheritance. LRRK2 or SNCA are associated with Autosomal Dominant inheritance. Likewise, PARK7, PINK1, or PRKN gene are associated with Autosomal Recessive.

Matt Farrer made several discoveries of the LRRK2 gene. People with PD have about 1-2% chance of having the LRRK2 gene. Previously, I mentioned that around 1 million people will have Parkinson’s disease in the U.S by 2020. Therefore 1-2% of 1 million works out to 10,000 people in the U.S with this mutation who have Parkinson’s. Some people may ask if only 10,000 people in the U.S are affected why focus on this gene? Because “LRRK2 (leucine-rich repeat kinase 2) is the most common genetic contributor to Parkinson’s disease”. For clarification, those that have the LRRK2 gene are more likely to develop Parkinson’s then people that have any of the other genes. By studying and researching LRRK2 we will discover more about the inheritance of Parkinson’s disease.

Intro to the Data

Inheritance is exactly what I am researching this summer by using computational and statistical methods.For example, I am given data, which I then clean, and analyze through multiple programs in order to calculate PRS or Polygenetic Risk Scores for individuals currently with Parkinson’s and Alzheimer’s. The risk score based on inheritance. Next time I will dive deep into the data, and exactly what it means to calculate PRS.