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Alzheimer's disease (AD) and Parkinson's disease (PD) are genetically heterogeneous. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) genes may modify the risk of these disorders. We investigated whether common polymorphisms present in these genes operate as risk factors for AD and PD in Finnish subjects, independently or in concert with the apolipoprotein E 4 allele (APOE 4). Eighty late onset sporadic AD patients, 53 PD patients (34 of whom had concomitant AD pathology), and 67 control subjects were genotyped for the insertion (I)/deletion (D) polymorphism of DCP1 and the K variant of BCHE. In logistic regression analysis, the DCP1 *I allele in combination with APOE 4 significantly increased the risk of AD (OR 30.0, 95% CI 7.3-123.7), compared to subjects carrying neither of the alleles. Similar analysis showed that the risk of AD was significantly increased in subjects carrying both the BCHE wild type (*WT/ *WT) genotype and 4 (OR 9.9, 95% CI 2.9-33.8), compared to those without this BCHE genotype and 4. Further, the risk of PD with AD pathology was significantly increased for carriers of DCP1 *I and 4 (OR 8.0, 95% CI 2.1-31.1). We thus conclude that, in Finns, interaction between DCP1 *I and 4 increases the risk of AD as well as of PD with coexisting Alzheimer pathology, which underlines the importance of the DCP1 I/D polymorphism in the development of Alzheimer neuropathology, whereas the wild type BCHE genotype in combination with 4 had a combined eVect with regard to the risk of AD. (J Med Genet 2000;37:766-770)

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