Session Information
Date: Wednesday, June 7, 2017
Session Title: Parkinson's Disease: Cognition
Session Time: 1:15pm-2:45pm
Location: Exhibit Hall C
Objective: We investigated whether carrying one copy of the protective haplotype “KL-VS” of the longevity gene KLOTHO is associated with better cognitive functioning and/or attenuated CSF biomarker changes in Parkinson’s disease (PD).
Background: Cognitive impairment from PD poses a major challenge for which we have no effective medical treatments. Identifying genetic variations associated with brain resilience could help elucidate mechanisms that counter PD. Klotho is a pleiotropic protein. At higher levels, klotho extends lifespan, enhances cognition, and counters neurodegenerative disease-related toxicities in model organisms. In humans, KL-VS heterozygosity associates with increased klotho levels, longevity, and better executive cognition in normal aging. In this study, we investigated whether KL-VS heterozygosity associates with resilience in PD.
Methods: The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing longitudinal study in patients with newly diagnosed PD and matched healthy controls (HC). Data used in the preparation of this abstract was obtained from the PPMI database (www.ppmi-info.org/data). We evaluated KL-VS heterozygous frequencies, baseline cognitive function, and CSF biomarker levels in HC and PD subjects, based on KL-VS status.
Results: The frequency of KL-VS non-carriers and heterozygotes was similar between HC and PD subjects. In PD, KL-VS heterozygotes showed better baseline semantic and phonemic fluency compared to non-carriers, among a myriad of tests. As anticipated, CSF α-synuclein levels were lower in all PD compared to HC subjects. However, in KL-VS heterozygotes above age 50, CSF α-synuclein was unchanged between HC and PD; in contrast, non-carriers showed decreased α-synuclein levels in PD compared to HC. We are further evaluating effects of age and time on KL-VS associations.
Conclusions: We found that KL-VS heterozygosity was associated with (1) better cognitive performance in specific domains and (2) attenuation in the decrease in CSF α-synuclein in PD patients. These findings suggest a role for klotho in conferring resilience against PD and may open new therapeutic pathways.
To cite this abstract in AMA style:
N. Luthra, J. Ostrem, D. Dubal. Variation in Longevity Gene KLOTHO Associates with Measures of Resilience Against Parkinson’s Disease [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/variation-in-longevity-gene-klotho-associates-with-measures-of-resilience-against-parkinsons-disease/. Accessed June 15, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/variation-in-longevity-gene-klotho-associates-with-measures-of-resilience-against-parkinsons-disease/