CYP2D6 is associated with Parkinson's disease but not with dementia with Lewy Bodies or Alzheimer's disease

The similarities between the clinical and pathological findings of dementia with Lewy Bodies (DLB) with Alzheimer's disease and Parkinson's disease ar e complex, and their significance for pathogenesis is unresolved It is like ly that DLB shares common disease determinants with both Alzheimer's diseas e and Parkinson's disease. Clinically DLB shows the presence of dementia si milar, though not identical, to that found in Alzheimer's disease. A parkin sonian movement disorder is present in a proportion of DLB cases, Pathologi cally DLB shows senile plaques, as with Alzheimer's disease, and also subst antia nigra neurone loss and Lewy bodies, as with Parkinson's disease, At a genetic level, DLB shows an elevated Apolipoprotein E epsilon 4 frequency as described in Alzheimer's disease, but this is absent in Parkinson's dise ase. An elevated frequency of the CYP2D6*4 allele has been found in Parkins on's disease and we have therefore genotyped a large series of clinically a nd neuropathologically confirmed cases of DLB, Alzheimer's disease, Parkins on's disease and age-matched control individuals for the CYP2D6*4 allele, W hilst an elevated frequency of the CYP2D6*4 allele was found in Parkinson's disease, no such elevations were found in DLB or Alzheimer's disease, Stra tification of the CYP2D6*4 allele with respect to the Apolipoprotein E epsi lon 4 also did not show any significant associations with the CYP2D6*4 alle le, The CYP2D6*4 allele is not a major genetic determinant of DLB and the r esults place DLB with Alzheimer's disease rather than Parkinson's disease o n a genetic level, Pharmacogenetics 9:31-35 (C) 1999 Lippincott Williams & Wilkins.