Abstract
The H1 haplotype of the microtubule-associated protein tau gene (MAPT) is associated with an increased risk of Parkinson disease (PD) compared with the H2 haplotype, but its effect on Lewy body (LB) formation is unclear. In this study, we compared the MAPT haplotype frequency between pathologically confirmed PD patients (n = 71) and controls (n = 52). We analyzed Braak LB stage, Braak neurofibrillary tangle (NFT) stage, and CERAD amyloid score by haplotype. We further tested the association between MAPT haplotype and semi-quantitative counts of LBs, NFTs, and neuritic plaques (NPs) in multiple neocortical regions. Consistent with previous reports, PD cases had an increased likelihood of carrying an H1/H1 genotype compared to controls (OR = 5.72, 95 % CI 1.80–18.21, p = 0.003). Braak LB, Braak NFT and CERAD scores did not differ by haplotype. However, H1/H1 carriers had higher LB counts in parietal cortex (p = 0.02) and in overall neocortical LBs (p = 0.03) compared to non-H1/H1 cases. Our analyses suggest that PD patients homozygous for the H1 haplotype have a higher burden of neocortical LB pathology.
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Abbreviations
- CERAD:
-
Consortium to establish a registry for Alzheimer’s Disease
- LB:
-
Lewy body
- MAPT:
-
Microtubule-associated protein tau
- NFT:
-
Neurofibrillary tangle
- PD:
-
Parkinson disease
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Acknowledgments
We thank Codruta Chiuzan and Jimmy Duong for assistance with statistical analysis. This project was funded by the Parkinson’s Disease Foundation (LNC, Lucien Cote Early Investigator Award to OAL), a Pilot Research Award (CAMPR-BASIC to JFC, OAL) and use of Biostatistics Core Resource from the Columbia University Irving Institute (NIH UL1-TR00040), and by the NINDS (K08-NS070608 for OAL, P50NS038370 for LNC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Robakis, D., Cortes, E., Clark, L.N. et al. The effect of MAPT haplotype on neocortical Lewy body pathology in Parkinson disease. J Neural Transm 123, 583–588 (2016). https://doi.org/10.1007/s00702-016-1552-3
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DOI: https://doi.org/10.1007/s00702-016-1552-3