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 are complex, and their significance for pathogenesis is unresolved. It is likely that DLB shares common disease determinants with both Alzheimer's disease and Parkinson's disease. Clinically DLB shows the presence of dementia similar, though not identical, to that found in Alzheimer's disease. A parkinsonian movement disorder is present in a proportion of DLB cases. Pathologically DLB shows senile plaques, as with Alzheimer's disease, and also substantia nigra neurone loss and Lewy bodies, as with Parkinson's disease. At a genetic level, DLB shows an elevated Apolipoprotein E epsilon4 frequency as described in Alzheimer's disease, but this is absent in Parkinson's disease. An elevated frequency of the CYP2D6*4 allele has been found in Parkinson's disease and we have therefore genotyped a large series of clinically and neuropathologically confirmed cases of DLB, Alzheimer's disease, Parkinson's disease and age-matched control individuals for the CYP2D6*4 allele. Whilst 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. Stratification of the CYP2D6*4 allele with respect to the Apolipoprotein E epsilon4 also did not show any significant associations with the CYP2D6*4 allele. The CYP2D6*4 allele is not a major genetic determinant of DLB and the results place DLB with Alzheimer's disease rather than Parkinson's disease on a genetic level.
Atkinson
A
A
Medical Research Council Neurochemical Pathology Unit, Institute for the Health of the Elderly, Newcastle General Hospital, Newcastle upon Tyne, UK.
Singleton
A B
AB
Steward
A
A
Ince
P G
PG
Perry
R H
RH
McKeith
I G
IG
Fairbairn
A F
AF
Edwardson
J A
JA
Daly
A K
AK
Morris
C M
CM
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001483:Base Sequence; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D017931:DNA Primers; D003704:Dementia / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017931:DNA Primers; D019389:Cytochrome P-450 CYP2D6