Pesticide Exposure and Parkinson's Risk

Pesticides and related lifestyle factors, exposure to well water containing ground run-off, farming using pesticides, rural living are repeatedly reported risk factors for Parkinson's disease. There are few family-based studies looked at those relationships. Is there a genetic connection?

In 1992 the results of a study conducted at the University of Calgary were published. It involved 130 residents with neurologist-diagnosed ideopathic Parkinson's and 260 controls to determine whether agricultural or occupational use of pesticides had an association with increased PD risk. The study looked at field crop farming, grain farming, herbicide or insecticide usage and exposure variables. The ultimate conclusions were that there was a dose-response relation to the PD risk through field and grain crop farming and also occupational use of herbicides.

In 1998 the results of a study by the Department of Neurology at the Henry Ford Health System in Detroit performed a similar study adding cigarette smoking to the mix. The conclusions were similar: a significant association of occupation-exposure (farming) and herbicides and insecticides but no increased risk of PD with rural or farm residence or well water usage. They concluded that farming or pesticide exposure alone did not appear to be a risk factor.

A study was published in the June 2006 issue of Movement Disorders by Dr Demetrius "Jim" Maraganore, Mayo Clinic Professor of Neurology whose principle research interest is to identify the causes of Parkinson's disease, through molecular genetic and epidemiologic approaches. That study confirmed conclusions of prior studies, "What we think may be happening is that pesticide use combines with other risk factors in mens environment or genetic makeup, causing them to cross over the threshold into developiing the disease." Moreover, "One possibility is that to get Parkinson's disease, you not only have to be exposed to pesticides, but you have to be genetically predisposed" He also noted that pesticide exposure accounts for only 10-15% of Parkinson's cases.

In the Mayo Clinic study, investigators contacted all of the Olmsted County, MN residents who had been diagnosed with PD between 1976 and 1995. They were then assigned control matches. The phone interview was to determine the exposure to chemical products: farming, non-farming work or hobbies. Although unable to determine the exact exposure levels the study did conclude that men with PD had 2-4 times more exposure to pesticides than the controls.

In 2006 research at the University of North Dakota, at Emory University and at Harvard University had similar conclusions that pesticide exposure appears to cause a loss of neurons in particular areas of the brain.

Researcher's at Duke University Medical Center and the University of Miami Miller School of Medicine examined 319 cases and 296 relative and other controls. They recorded associations of direct pesticide application, well-water consumption, and farming residences/occupations. They controled for age at examination, sex, cigarette smoking and caffeine consumption.

Individuals with PD were significantly more likely to report direct pesticide application than their unaffected relatives. Associations of direct pesticide application did not vary by gender.
When classifying pesticides by a functional type, both insecticides and herbicides were found to significantly increase the risk of PD: Two specific classes of insecticides, organochlorines and organophosphorus, were significantly associated with PD.

Sources:
Pesticide exposure and risk of Parkinson's disease:
A family-based case-control study
Hancock,Martin,Mayhew etal 8 March, 2008
Duke University Medical Center
University of Miami Milleer school of Medicine

http://www.voanews.com/english/archive/2006-06/2006-06-24-voa21.cfm
http://www.ncbi.nlm.nih.gov/pibmed/9595985
http://www.ncbi.nlh.gov/pubmed/17708091?ordinalpos=1&tool=EntrezSystem2.PEnt
http://www.ncbi.nlm.nih.gov/sites/entrez

Mayo discovery could cure Parkinson's, Lou Gehrig's

Scientists have discovered the defect that damages the brain's neurons

By Jeremy Cox

Story updated at 5:37 AM on Monday, Jan. 12, 2009

Of the billions of people who have ever walked this planet, only about 100 have been diagnosed with Perry syndrome.

So why would an international team of scientists led by a Mayo Clinic Jacksonville researcher spend seven mostly frustrating years looking into obscure corners of the human genome in search of its cause?

For the chance to unlock a key biological doorway that could lead to better treatments - or even a cure - for Parkinson's disease, Lou Gehrig's disease and depression.

In May, the team discovered what it was looking for, complete with a eureka moment. The findings appear today in the online edition of Nature Genetics and in the journal's February issue.

"To me, it's one piece in the puzzle of the whole picture of neurodegeneration," said Matt Farrer, the study's lead author and a Mayo Jacksonville neuroscientist.

The team's hunt uncovered among Perry syndrome patients a genetic defect in the protein that serves as the molecular motor for all of the body's cells. For reasons still unknown, the defect only affects neurons, or brain cells, in the midbrain, the part that controls muscle movement.

Perry syndrome was first recognized in 1975 as a distinct illness. Its symptoms are so similar to Parkinson's disease that doctors didn't realize for decades that something else was to blame for their patients' deterioration, Farrer said.

A person with the Perry defect typically sees the first signs around 50 years old. The syndrome begins with the onset of depression so devastating that one-third of patients commit suicide.

Those who survive the first stage, though, face a grim decline: Parkinson's-like symptoms and weight loss, followed by difficulty breathing and loss of bowel control. Most patients die within two to 10 years.

Farrer and the other researchers analyzed blood samples taken from four Perry syndrome-prone families. In all, the study included 40 people from Canada, France, Japan and the United States.

What followed were months of eye-blurring analysis in which researchers worked their way down the entire universe of genetic possibilities to the basic building blocks of DNA - nucleotides.

Just one variation out of billions - that's what Jenny Kachergus was looking for that day in May when a colleague in the Mayo lab called her over to look at a computer screen.

All the research analyst needed to see was one out-of-place line on a graph jammed with lines to know what she was looking at.

"Our jaws just dropped to the floor," Kachergus recalled last week.

The line showed a mutation in a group of proteins called dynactin, the cell motor. As far as Farrer can tell, the genetic defect causes neurons to go haywire and eventually die.

Erika Holzbauer, a University of Pennsylvania scientist who wasn't involved in Farrer's study, called the finding "exciting."

"That hopefully will give us clues as to why these cells are uniquely vulnerable to loss of function of that protein," she said. "If we have a clue of what's going wrong, we have the key to fixing what's wrong."

The next step is learning exactly what happens in the dying brain cells, said Holzbauer, who plans to work with Farrer on a component of that effort.

Farrer's team included researchers from Canada, France, Japan and Turkey. Their work was backed by the Pacific Alzheimer Research Foundation of British Columbia and the National Institutes of Health.

jeremy.cox@jacksonville.com, (904) 359-4083

Uncovering Neurodegenerative Diseases

Reported January 13, 2009

(Ivanhoe Newswire) -- Scientists have discovered a genetic defect that may help explain the cause of many neurodegenerative disorders, including Parkinson's disease.

Researchers studies eight families worldwide to uncover the genetic defect that causes depression and parkinsonism in a disorder called Perry syndrome. Sufferers of the disease experience depression, stiffness, severe weight loss, and difficulty breathing. Symptoms of the fatal and rapidly progressing disease usually occur in the mid-40s.

Those with Perry syndrome have mutations in a genetic area essential to the movement of molecular "cargo" inside brain cells. The mutations were forced along a "train" that basically couldn't stop.

Such a finding is crucial to understanding other neurodegenerative diseases, experts say. It suggests a break down among cell's transportation grid may be the cause of underlying neurodegeneration.

Comprehending why some neurons are vulnerable to disease and brain disorders while others are not is one of the greatest mysteries in neuroscience, says Matthew Farrer, Ph.D., a professor of neuroscience at Mayo Clinic. "These findings suggest that trafficking of specific cargoes inside brain cells may be a general problem in a variety of neurodegenerative diseases, depression, and other disorders," Dr. Farrer, Ph.D., neuroscience professor at Mayo Clinic, was quoted as saying.

The discovery of mutations in Perry syndrome has allowed researchers to shed light on depression, metabolic syndromes, sleep deprivation and even Alzheimer's disease.

Source: Nature Genetics, published online January 11, 2009

Discovery could benefit Parkinson's disease sufferers

EPG Online News
07 Jan 2009

A new study into the role of mechanisms associated with neurodegenerative diseases could benefit Parkinson's disease sufferers, it has been revealed.

Research undertaken at the University of Quebec and Montreal, Canada, by PhD student Sonia Do Carmo has highlighted the protective and reparative function of apolipoprotein D, more commonly known as ApoD.

Ms Do Carmo's discovery could mean the implementation of new treatments for diseases such as Parkinson's, dementia and multiple sclerosis.

Commenting on the study, professor Eric Rassart, who led an initial study into the effectiveness of ApoD, said that the next step was to "understand the action of the protein".

"Only then will we be able to think about creating a drug to prevent these types of diseases and to slow their progression," he said.

Professor Rassart added that, because so little was known about the mechanisms involved in neurodegenerative diseases, Ms Do Carmo's discovery represented a "significant breakthrough".

It is estimated that there are three to four million people in the US who have Parkinson's disease without it being diagnosed.

NPH can mimic Alzheimer's disease

Thursday, January 01, 2009 | 10:26 PM

By Carolyn Johnson

SAN FRANCISCO (KGO) -- Millions of Americans suffer from Alzheimer's disease, but a small percentage may have been misdiagnosed. They suffer from a condition with symptoms that are almost identical.

Ed Ferguson never thought he'd see this day.

"I just figured I was destined to spend the rest of my life in a wheelchair," said Ed Ferguson.

Now the 74-year-old is walking, talking and remembering again.

"I couldn't go to my kids, see my grandkids, my great-grandkids, and now I can," said Ferguson.

Ed has a disorder called Normal Pressure Hydrocephelus, or NPH. That's when your body produces too much cerebral spinal fluid that doesn't drain out of your brain as it should.

NPH often begins age 55. Hundreds of thousands of people suffer from it, but it's often misdiagnosed, because it both mimics Alzheimer's and Parkinson's disease.

"Patients may just think, well, it's just old age, or problems associated with old age and may not realize it's progressive and debilitating until three or four years later," said Dr. Jeff Chen from Pacific Neurosurgical.

Ed was lucky. His primary physicians noticed some classic NPH symptoms.

"I couldn't move this foot. If I stood up it would be like it was nailed to the floor or standing in some gum," said Ferguson.

He turned to Dr. Chen, a West Coast specialist in the syndrome. A shunt was placed through his skull, draining the fluid from his brain into his abdomen. The next day, Ed was different man.

"Remarkable. I mean, God, I could think again, I could talk reasonably with people. I could move," said Ferguson.

His wife Elva still can't believe it.

"It is absolutely amazing. It really is. It's so different that you can't explain it," said Ed's wife Elva Ferguson. "We'll do some fun things, you know, I don't think we'll be dancing again, but I hope it could happen."

"You just can't believe the change it's made in my life," said Ferguson.

While NPH can mimic diseases like Alzheimer's and Parkinson's, experts say three symptoms stand-out -- dementia, incontinence and especially difficulty moving the feet or walking.