23. 24. zyxwvutsrqponm 25. 26. 27. of the cynomologous monkey apolipoprotein cDNA. Nucl Acid Res 1989;17:1778 Horiuchi K, Tajima zyxwvutsrqp S, Menju M, Yamamoto A. Structure and expression of mouse apolipoprotein E gene. J Biochem 1989; 106:98-110 Selkoe DJ, Bell DS, Podiisny MB, et al. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer disease. Science 1987;235:873-877 Noguchi S, Murakami N, Yamada N. Apolipoprotein E geno- type and Alzheimer’s disease. Lancet 1993;342:737 Strittmatter WJ, Weisgraber KH, Huang D, et al. Proc Natl Acad Sci USA 1993;90:8098-8102 Menzel H-J, Kladetzky RG, Assmann G. Apolipoprotein E polymorphisms and coronary artery disease. Arteriosclerosis 1983;3 :3 10-3 15 Parkinson’s Disease and Brain Levels of Organochlorine Pesticides Lora Fleming, MD, MPH,* John B. Mann, MS,* Judy Bean, PhD,* Thomas Brigble, PhD,” and Juan R. Sanchea-Ramos, PhD, MDtt zyxwvuts Epidemiological studies have suggested an etiologic re- lationship between pesticide exposure and Parkinson’s disease (PD).Organochlorine pesticides were assayed in postmortem brain samples from 20 PD, 7 Alzheimer’s disease (AD), and 14 nonneurological control cases. The three groups were similar in age at death, sex, and demo- graphic variables. Only two of 16 pesticide residues screened were detected. A long-lasting residue of DDT (pp-DDE)was found in the majority of cases of PD and AD, zyxwvutsr as well as in all the control cases; pp-DDT was sig- nificantly more likely to be found in AD controls than the PD cases (Fisher’s exact two-tailed, zyxwvutsr p = 0.04). Diel- drin was detected in 6 of 20 PD brains, 1 of 7 AD, and in none of zyxwvutsrq 14 control samples. Despite the relatively small number of brains assayed, the association between Diel- drin and the diagnosis of PD was highly significant (p = 0.03). Dieldrin, a lipid-soluble, long-lasting mito- chondrial poison, should be investigated as a potential etiological agent of Parkinsonism. Fleming L, Mann JB, Bean J, Briggle T, Sanchez-Ramos JR. Parkinson’s disease and brain levels of organochlorine pesticides. Ann Neurol 1%4;36: 100-103 From the Departments of ‘Epidemiology and Public Health, and tNeurology, University of Miami School of Medicine, and $Geriat- ric Research and Clinical Center, Miami VA Medical Center, Miami, FL. ReceiveJ Apr 13, 1993, and in revised form Oct 25, Nov 29, and Dec 21. Accepted for publication Dec 22, 1093. Address correspondence to Dr Sanchez-Ramos, Department of Neurology, University of Miami School of Medicine, 1501 NW 9 Ave, Miami, FL 33136. Epidemiologic studies point to a connection between pesticide exposure and Parkinson’s disease (PD) C1-91 (for reviews, see El-31). The prevalence of PD has increased in industrialized countries compared with newly industrialized or nonindustrialized nations; the prevalence appears to be increasing especially for early- onset PD. Other studies have found an increased risk of PD with a history of rural residence, especially for those persons with early-onset PD (i.e., < 50 yr old). And many of these persons had histories of drinking well water in their youth {4, 57. Case-control stuldies in China, Spain, and Canada have found a relationship between an increased risk of PD and pesticide and industrial chemical exposures { 1 J. Semchuck and co-workers {7], Butterfield and col- leagues [S], and Hubble and associates {9] found signih- cant risks of pesticide and herbicide exposures and PD. Many commonly used pesticides, such as the major- ity of the organophosphates, are not stored in the hu- man body. However, the organochlorines, such as zy 2,2- bis(p-chlorophenyl)-l, 1,l,-trichloroethane (DDT) and lindane, which had wide use in the United States until 1772, can still be Csund in humans, from environmen- tal contamination, and can be measured in adipose- containing tissues. Furthermore, other organochlorines from both lifetime occupational and environmental ex- posures can be found in adipose tissue of humans throughout the world {lo, 111. The objective of this study was to screen human brain samples for organochlorine pesticides and to de- termine whether there was an association benveen a specific pesticide and PD. Materials and Methods Forty-one brain specimens were analyzed (Table I). These brains were obtained through the University of Miami/Na- tional Parkinson Foundation Brain Endowment Bank and the Brain Tissue Resource Center at McLean Hospital (Belmont, MA). Twenty of the 41 brain specimens were cases of PD and 21 were controis. Among the 21 control specimens, 7 were pathologically confirmed Alzheimer’s disease (AD) and 14 were “normal” (i.e., either no obvious neuropathology or atherosclerotic disease or both). Diagnosis was based on pathological criteria for PD (loss of nigral neurons and pres- ence of Lewy bodies) and CERAD criteria for definite AD 112). Two of the PI> cases were not classic Lewy-body Par- kinson’s disease; 1 case exhibited marked cortical atrophy and gliosis, in addition to neuronal loss in the substantia ni- gra, and a second case exhibited senile plaques and neurofi- brillary tangles as well as neuronal loss and Lewy bodies, suggesting a dual diagnosis of PD and AD. (These 2 cases are referred to as “PD + ” later in the text). There was limited clinical information available on all the subjects. The majority of brain samples were from cortex (frontal or occipital) and, in about 50% of the subjects, samples of white matter (corpus callosum) were studied. “Mixed” cortex con- sisted of individual samples of frontal and occipital cortex from the same brain, which were combined for analysis because the quantity was too small to allow for individual analysis. 100 Copyright zyxwvutsr 0 1994 by the American Neurological Association