Book contents
- Frontmatter
- Contents
- Contributors
- Foreword
- Acknowledgements
- Biographical note on F. H. Lewy
- Abbreviations
- Group photograph
- Introduction
- Part one Clinical issues
- Part two Pathological issues
- 15 Pathological significance of Lewy bodies in dementia
- 16 Tautological tangles in neuropathologic criteria for dementias associated with Lewy bodies
- 17 What is the neuropathological basis of dementia associated with Lewy bodies?
- 18 Cytoskeletal and Alzheimer-type pathology in Lewy body disease
- 19 Diffuse Lewy body disease within the spectrum of Lewy body disease
- 20 Temporal lobe immunohistochemical pathology for tangles, plaques and Lewy bodies in diffuse Lewy body disease, Parkinson's disease, and senile dementia of Alzheimer type
- 21 Pathological and clinical features of Parkinson's disease with and without dementia
- 22 Dementia with Lewy bodies: relationships to Parkinson's and Alzheimer's diseases
- 23 What do Lewy bodies tell us about dementia and parkinsonism?
- 24 Pathogenesis of the Lewy body
- 25 Altered tau processing: its role in development of dementia in Alzheimer's disease and Lewy body disease
- 26 Cytoskeletal pathology in Alzheimer's disease and Lewy body dementia – an epiphenomenon?
- 27 Genetic correlations in Lewy body disease
- Résumeacute; of pathological workshop sessions
- Part three Treatment issues
- Appendices
- Index
- Plate section
27 - Genetic correlations in Lewy body disease
from Part two - Pathological issues
Published online by Cambridge University Press: 06 July 2010
- Frontmatter
- Contents
- Contributors
- Foreword
- Acknowledgements
- Biographical note on F. H. Lewy
- Abbreviations
- Group photograph
- Introduction
- Part one Clinical issues
- Part two Pathological issues
- 15 Pathological significance of Lewy bodies in dementia
- 16 Tautological tangles in neuropathologic criteria for dementias associated with Lewy bodies
- 17 What is the neuropathological basis of dementia associated with Lewy bodies?
- 18 Cytoskeletal and Alzheimer-type pathology in Lewy body disease
- 19 Diffuse Lewy body disease within the spectrum of Lewy body disease
- 20 Temporal lobe immunohistochemical pathology for tangles, plaques and Lewy bodies in diffuse Lewy body disease, Parkinson's disease, and senile dementia of Alzheimer type
- 21 Pathological and clinical features of Parkinson's disease with and without dementia
- 22 Dementia with Lewy bodies: relationships to Parkinson's and Alzheimer's diseases
- 23 What do Lewy bodies tell us about dementia and parkinsonism?
- 24 Pathogenesis of the Lewy body
- 25 Altered tau processing: its role in development of dementia in Alzheimer's disease and Lewy body disease
- 26 Cytoskeletal pathology in Alzheimer's disease and Lewy body dementia – an epiphenomenon?
- 27 Genetic correlations in Lewy body disease
- Résumeacute; of pathological workshop sessions
- Part three Treatment issues
- Appendices
- Index
- Plate section
Summary
Summary
A subpopulation of Alzheimer's disease (AD) patients with neocortical Lewy bodies (LB) and subtle extrapyramidal signs, a clinical-pathological phenotype that we have termed the Lewy body variant of AD (LBV), has an increased allele frequency of APO E e4 allele, similar to that observed in AD subjects without LB (pure AD), although individuals homozygous for the APO E e4 allele are overrepresented in pure AD as compared with age-matched controls, but not as markedly in subjects with LBV. Furthermore, we have found that the CYP2D6B mutant allele, a risk factor for Parkinson's disease (PD), is overrepresented in LBV, a finding that has been controversial. To further evaluate the involvement of the CYP2D6 locus in LBV, the Xbal restriction fragment length polymorphisms (RFLP) of CYP2D6, 44 kb, 15/9 kb, and 13 kb (D mutation), were examined for association with LBV. The 15/9-kb RFLP was found in pure AD or in non-AD individuals but was not found in LBV. On the other hand, the 44-kb Xbal RFLP in the presence of the concomitant CYP2D6B mutant allele was strongly associated with LBV. The tightest association with LBV was found in the combination of the 44-kb RFLP and CYP2D6B mutant allele in the absence of the 15/9-kb RFLP. A CYP2D6 deletion mutation D, detected as 13-kb RFLP, was not linked to LBV. Taken together, these findings suggest that the inactivation of CYP2D6 represented by the B or D mutation may not per se be the risk factor for LBV but that an independent mutation or allele linked to the CYP2D6B mutation and the 44-kb Xbal RFLP (such as NF-H or PDGfb genes) might be associated with LB formation in AD.
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- Dementia with Lewy BodiesClinical, Pathological, and Treatment Issues, pp. 336 - 349Publisher: Cambridge University PressPrint publication year: 1996
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