The effect of MAPT haplotype on neocortical Lewy body pathology in Parkinson disease.
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.
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.|Departments of Neurology, Yale School of Medicine, New Haven, CT, USA.
Daphne
D
Robakis
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Etty
E
Cortes
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Lorraine N
LN
Clark
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Jean Paul G
JP
Vonsattel
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.|Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Tuhin
T
Virmani
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Roy N
RN
Alcalay
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|Departments of Pathology and Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
John F
JF
Crary
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA. ol2102@cumc.columbia.edu.
Oren A
OA
Levy
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006239:Haplotypes; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D008297:Male; D019579:Neocortex / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D016875:tau Proteins
Lewy body; MAPT haplotype; Neuropathology; Parkinson’s disease; Tau