Dieldrin and organochlorines in Parkinson's brains

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Fleming, Mann, Bean, Briggle and Sanchez-Ramos (University of Miami, 1994); Freda Corrigan, Wienburg, Shore, Susan Daniel and David Mann (2000; Corrigan's listed address is a Scottish primary care trust); Jason Richardson, Gary Miller and colleagues (Emory University, 2006); Richardson, Shalat, German and colleagues (Rutgers and UT Southwestern, 2009). Funders are not stated in the abstracts.

What happened

Organochlorines are long-lived, fat-soluble insecticides, mostly banned in the West since the 1970s–80s. Like MPTP and rotenone (landmarks 2 and 13), they were suspected of poisoning mitochondria.

• 1994: 16 pesticide residues were screened in post-mortem brains of 20 people with Parkinson's, 7 with Alzheimer's and 14 controls. Only two were detected. Dieldrin was found in 6 Parkinson's brains, 1 Alzheimer's brain and no controls (p = 0.03).
• 2000: in the substantia nigra (the dopamine region), lindane (gamma-HCH) was higher in Parkinson's than in dementia with Lewy bodies, Alzheimer's or control brains, and dieldrin was higher than in Alzheimer's or control brains.
• 2006: mice exposed to low dieldrin doses before birth had more dopamine transporter and VMAT2 protein, and lost more dopamine after a later MPTP dose. Males were affected more.
• 2009: in blood serum, beta-HCH (another organochlorine) was detected in 76% of 50 Parkinson's patients, against 40% of 43 controls and 30% of 20 Alzheimer's patients (odds ratio against controls 4.39, 95% CI 1.67–11.6).

Why it moved us toward a cure

It pointed to a specific, persistent chemical class and gave a biological mechanism (the transporter changes), supporting prevention through exposure limits. Studies in farmers (landmark 25) came later and looked at different chemicals.

Outcome

Open. All studies were small. Brain levels measured after death cannot show that exposure came first, and the 1994 result rests on 6 positive brains.

Sources

• Fleming et al., Ann Neurol 1994;36:100–103, DOI 10.1002/ana.410360119
• Corrigan et al., J Toxicol Environ Health A 2000;59:229–234, DOI 10.1080/009841000156907
• Richardson et al., FASEB J 2006;20:1695–1697, DOI 10.1096/fj.06-5864fje
• Richardson et al., Arch Neurol 2009;66:870–875, DOI 10.1001/archneurol.2009.89
• Not yet verified: full texts (abstracts only); the 2006 human brain comparison once reported in the press (14 cases v 12 controls) was not found in the abstract and is left out; the Corrigan group's institution.