Objective: To study the Microtubule-Associated Protein Tau (MAPT) H1/H2 haplotype contribution to clinical manifestation of Parkinson’s disease (PD) in an Ashkenazi Jewish (AJ) cohort, focusing on subgroups of Leucine-Rich Repeat Kinase 2 (LRRK2) p.G2019S and Glucocerebrosidase (GBA) p.N370S variant carriers.

Background: An association of the MAPT H1/H2 haplotype with PD susceptibility has been reported, but its effect on clinical phenomenology may be modulated by additional factors.

Method: The Sheba Medical Center AJ cohort was studied, including PD patients carrying the N370S GBA variant (and negative for LRRK2 p.G2019S variant, GBA-PD, n=79), LRRK2 p.G2019S variant carriers (negative for GBA variants, LRRK2-PD, n= 65) carriers of neither variant (MNPD, n=465; 200 of them had clinical details), and healthy controls (HC, n=483). MAPT H1/H2 haplotype frequencies were compared between the groups. In addition, we evaluated the association of this haplotype with several clinical features: age at PD onset, Hoehn & Yahr score at last visit, tremor as first sign, prevalence of motor fluctuations and dyskinesias, presence of freezing of gait, REM sleep behavior (RBD), psychosis and dementia.

Results: There was no significant difference in H1/H2 frequencies between MNPD and the HC (p=0.11).
The MAPT haplotype status had a small effect, if any, on any of the disease related features studied, except for RBD in the MNPD group (H2 was more frequent among patients with RBD, compared to H1; p=0.02) In all other parameters, no differences were found between MAPT H1 and H2 haplotype.

Conclusion: In this AJ PD cohort, H1/H2 MAPT haplotype was not associated with PD risk or clinical features.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/h1-h2-mapt-haplotype-and-parkinsons-disease-in-an-ashkenazi-jewish-cohort/