“Environment and Parkinson’s disease” – Webinar Notes

Speaker: Beate Ritz, MD, PhD, epidemiologist, Center for Occupational and Environmental Health, UCLA, Los Angeles, California

Webinar Host: PD Active

Webinar Date: January 8, 2021

Summary by: Joëlle Kuehn, Stanford Parkinson’s Community Outreach

Environmental factors and neurodegeneration:

Industrially produced chemical pesticides use started in the 1950’s, and the use/consumption and production has increased dramatically since then

China uses and produces the most pesticides (5-6x next highest consumer (US))

Pesticide use reporting system – California:

Called California Agricultural Pesticide Use Reports

Created in 1972

Can track Paraquat use in Central Valley

Reports provide: county, exact location, application date, commodity (what they are planting), method (ground, etc.), how many acres the treated area is, how much product applied (in gallons), percentage, active ingredient of specific pesticide (in pounds)

Speaker and her students created maps based on that

In US, most use is herbicide, Paraquat is most used herbicide, highest used to be glyphosate but Paraquat is now used more because weeds are getting resistant to glyphosate

Insecticides are also concerning because they are intentionally neurotoxic – engineered to kill:

Way they kill is by poisoning the nervous systems

Won’t kill us directly like it will insects, but there are long-term chronic effects on our nervous system. Neurodegeneration may be one of them

Fungicides are toxic to nerve cells

Why worry about pesticides:


Insecticides previously and currently used in agriculture have known acute neurotoxicity

1999-2000 NHANES (National health and nutritional exam studies):

US population survey (6-59 years old) urine pesticide metabolites show chlorpyrifos in 96% of samples, and Diazinon n 29% of samples

Chlorpyrifos was widely used indoors for insects, now banned for indoor and garden use, but not for agricultural use

Diazinon found in air in communities around where the pesticides are used

Use of these has died down, and new ones (neonicotinoids) are used to replace them


Insecticides currently widely used in agriculture

2015-2016 NHANES. US population survey urine pesticide metabolites show half of US population 3+ years of age are exposed to neonicotinoids

Pesticides linked to PD onset:

Many studies done on link, and studies show overwhelmingly that there is an increased risk of having PD if you report having used pesticides or specific pesticides in your life time

Exposed have a higher risk of PD (90% higher risk with pesticide exposure)

Rural living increases risk of PD by 60%

Farming increases risk of PD by 40%

Knowing which pesticides is important

Parkinson’s, Environment and Gene study (PEG):

Funded by NIH, and national institute of environmental health sciences

Case-control study in 3 rural California counties that enrolled and interviewed:

849 idiopathic (not genetic) PD newly diagnosed cases

Were clinically evaluated by UCLA movement disorder neurologists 1-5 times over a 14 year period. Have onset data and follow up data because they were followed over time

1,011 population controls and 193 unaffected sibling/household controls were used to compare


Blood: researched DNA, RNA, plasma, serum



Fecal samples

What do participants do – give data:

Residence: address, if they lived on a farm, what their water supply was, if they lived near fields or orchards, if they lived closer to the center of a town vs the margin of a town

Occupation: dates worked, title/company/address, street and cross streets, hours per week

Also use the California Agricultural Pesticide Use Reports since 1974

Created maps

Using person’s home address and work address, can see if overlaps areas where pesticides are used:

Especially Paraquat and Maneb

Both increase risk of PD in occupational and residential settings (80%)

This is relevant information and useful. Environmental Protection Agency (EPA) did something similar and Chlorpyrifos detected in 64% of all samples (468) in 2006 applied 14,252 kg in 1,217 applications

How do we identify “bad players”?:

MPTP: designer heroin contaminant that led to acute PD in young drug users in California in the 1980’s

MPTP destroys dopamine receptors – can be used to induce PD in mice

This is helpful as it provides animals to test on

Chemically looks like Paraquat, so can easily see the impact Paraquat has on the brain

Chemicals in well-water study:

Study looks into well-water consumption and PD in rural California

Pesticide runoff from fields may contaminate well water

Many participants used well water, and wanted to see water quality, and what is used around the wells

Found if there are water-soluble pesticides applied around the wells, you had individuals with a 68% increase in risk

If there are organophosphates applied around the well, individuals had a 71% increase in risk

If n-methyl carbamates, 24% increase in risk

All pesticides (of 26 researched) on average provide a 66% increase in PD risk

Gene-environment interactions with Paraquat herbicide:

See if people have genes that increase/decrease susceptibility to neurotoxic effects of pesticides

Genetics loads the gun for the disease, environment pulls the trigger:

Susceptibility is loading the gun

Environment pulls trigger

If gun is never loaded, wouldn’t have the risk, but if trigger isn’t pulled, wouldn’t have it either

Looked for people who are at risk genetically (DAT1 gene variants), and compare with Paraquat/maneb pesticide exposure:

DAT1 gene variants increase PD susceptibility with Paraquat/Maneb exposures

If hit with pesticides, risk increases

If have 2 or more genetic factors, risk increases 5 fold if combined with environmental exposure

2 or more genetic risk alleles + high environmental exposure is the worst possible outcome

Environment – environment (ExE) interactions and PD:

Environmental factors: Pesticides and head trauma

Head trauma has been hyothesiyed to increase the risk of PD

Head trauma/traumatic brain injury (TBI) was classified as severe enough that they were unconscious for 5 minutes at the minimum

Risk of developing PD with TBI but no Paraquat increased risk also

Risk of PD with TBI and Paraquat-exposure is 3x

Organophosphates (OP):

Insecticides that poisons the nervous system


Pesticide is metabolized in the body

Detoxified really fast (within 48 hours):

Get in, do damage, ge out

Hard to study because no trace in blood sample unless recent exposure, or chronic long term exposure

detoxified by paraoxonase activity of PON1 hydrolyzing enzyme

PON1 is enzyme detoxifies the insecticide that kills neurons. PON1’s ability to detoxify (enzyme activity) varies across populations:

Genetically different across populations

Some people have poor metabolizers or ultra rapid metabolizers, this is based on genetics

Ultra rapid can do it 4 times faster

Can classify/categorize population into poor metabolizers and high metabolizers

Low enzyme activity / metabolizing capacity increases risk greatly

Low metabolizing capacity and high exposure to chlorpyrifos: 3x risk

Low metabolizing capacity and high exposure to parathion: 2.5x risk

Different study: For household organophosphate pesticide use:

Frequent use of OP pesticides increases ratio by 1.03

Frequent use and having a slow metabolizer: increases risk ratio by 2.62

OPs also contribute to speed up cognitive decline in PD:

Over 5 years, -3.38 points on the MMSE score with high OP exposure

With no exposure, was only -1.35 points on the MMSE


Epigenetics: environment changes genes

Environment tells games whether to produce a messenger that then produces proteins

Environment can influence the hole message translation signaling

Back and forth of what you put in, and what the cell wants to do with it

Environment interacts with genetics of blood cells and composition of white blood cells

More granulocyte count in white blood cells for PD patients

Leads to questions such as If PD have more granulocytes, do they have to defend themselves more against infections?

Can look at what signals pesticides leave. Long-term exposure of organophosphates lead to signals of organophosphates found in the blood:

Very exciting because can now determine if pesticides have played a factor

Usually pesticides ar in and out within 48 hours and don’t leave traces of itself behind

Have now seen that there is a trace because can see that cells were fighting them in a very specific manner which left a “signature” of the agent

Changing face of PD:

New research: gastrointestinal problems are related to PD. New research on –

Does PD start in the gut?

Do gut bacteria slow down or promote PD symptoms and response to treatment?

Do pesticides in the environment disturb gut microbes and their role in PD? Are the toxic agents responsible for the composition of the bacteria in gut and the metabolites they generate that then go up into your bloodstream or up your nervous system into the brain

Have found differences in microbiome differences in PD patients and controls

Metabolite research:

We think metabolites are responsible for some of the toxicity

Some metabolites are different between PD patients and controls nad might actually tell us a lot more about what the toxins are and what PD patients are encountering compared to control patients

Decide which metabolites are toxic and which may be a defense mechanism in PD

Why is researching environment important?:

Setting standards for neurotoxic environmental exposures is needed to reduce PD risk

Need to know more about it

Need to move towards a “pesticidovigilance system” – after introduction of pesticides, company is responsible for monitoring side effects on population and protecting human health. Regulate pesticides like pharmaceuticals Phase 4 monitoring

Air pollution:


“Great Fog” in London in 1952 killed 12,000 people. Led to UK Clean Air Act of 1956 and restricted / banned coal burning in homes and industries

Donora, PA 1948 – 80 residents died and 4-5k (1/3) fell sick. Led to US Clean Air Act of 1970 set standards for 6 criteria pollutants including particulate matter

Environmental factors and neurodegeneration:

In 2010, World Health Organization considered air pollution as #9 most common risk factors to which healthy life years were lost and death was increase

In 2019, it was #4


Danish Parkinson’s disease study and air pollution

Funded by NIEHS

Many particles (micron sized) contain nano size particles and they go everywhere:

Mouse studies show that lungs and brain are affected

Animal models have shown quite bit that neurons are affected by the particles

Traffic related air pollution and PD risk increased:

All: 9%

In Copenhagen and suburbs: 16% increase

Provincial cities: 16%

Countryside: -1%

Looked at genetics as well. If at risk of inflammatory reactions, risk of PD is 3x greater

Looking forward, there is a need to reduce neurodegenerative diseases in aging populations through regulating air pollution and pesticide use.

Question & Answer:

Question: Is there a way to tell if one is a slow or fast metabolizer?

Answer: You can get yourself genotyped at a genetic lab to see if your PON1 gene has these variants, however I would be careful to recommend this. You can go two ways. First you can find out whether you are sensitive and susceptible, but you can also try to avoid exposure. Finding out if you are sensitive to organophosphates doesn’t tell you anything about if you are sensitive to neonicotinoids or another kind of pesticide.

Question: How many genes can people test for right now?

Answer: This is tricky because when we talk about genes, we talk of two different types of genes. One are the disease genes, and the other are the gene-environment interaction genes. Those aren’t disease genes. PON1 doesn’t give you PD. PON1 detoxifies agents like organophosphates and some other functions as well. What we are challenging with environmental exposures are our detoxification systems of cells. That is not what is being tested at all. What you are being rested for are the genetic variants that in families increase risk of getting PD. Not the variants that may keep you healthy if you are exposed to a toxin.