Abstract Details

Title Exploring the Impact of Parkinson Disease (PD) Susceptibility Genes in Elders without PD

Topic Movement Disorders

Presentation(s) S13 - (-)

Poster/Presentation
Number 006

Background Recent studies have identified numerous loci significantly associated with PD; however, little is known about the impact of these alleles on disease related clinical and pathologic outcomes in elders without a PD diagnosis.

Objective

Design/Methods We studied nearly 1,700 subjects (mean age=78) from the Religious Orders Study and Rush Memory and Aging Project with longitudinal clinical evaluations and a nested neuropathologic cohort including 700 brains. Genotypes were available for 18 single nucleotide polymorphisms previously associated with PD susceptibility from published genome-wide scans. The primary outcomes included a clinical summary measure of parkinsonism, based on a modified motor unified PD rating scale, and the presence of Lewy bodies or neuronal loss within the midbrain substantia nigra at autopsy. Linear or logistic regression analyses were adjusted for age and gender.

Results PD risk alleles at MAPT (p=6x10-4), CCDC62 (p=0.004), and MED13 (p=0.005) were associated with parkinsonian signs, even after excluding subjects with a clinical diagnosis of PD. In secondary analyses, MAPT and CCDC62 were predominantly associated with bradykinesia, whereas MED13 and another risk allele, SREBF were associated with gait impairment. Surprisingly, none of the PD susceptibility loci were associated with Lewy body pathology; however, LRRK2 (p=0.009), BST1 (p=0.04), and nominally MED13 (p=0.05) were related to nigral neuronal loss.

Conclusions Besides their established link to PD susceptibility, our results support a broader role for several risk loci in the development of mild parkinsonian motor signs and associated motor disability in older persons.

Authors/Disclosures
Joshua M. Shulman, MD, PhD, FAAN (Duncan Neurological Research Institute) PRESENTER	Dr. Shulman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Helis Medical Foudation. The institution of Dr. Shulman has received research support from National Institutes of Health.
	No disclosure on file
Aron S. Buchman, MD (Rush Alzheimer's Disease Center)	No disclosure on file
	No disclosure on file
Julie A. Schneider, MD, MS (Rush Alzheimer'S Disease Center)	Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Schneider has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for alnylam. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for apellis. Dr. Schneider has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for National Hockey League. The institution of Dr. Schneider has received research support from NIH. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a scientific advisor with Fondation Alzheimer, France.
David A. Bennett, MD (Rush University Medical Center)	Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Origent. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Study section, DMC, NACA Council with NIH. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a invited lectures with AMCs. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a invited paper with National Academy of Sciences. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a lecture with National Academy of Neuropsychology.
	No disclosure on file
Philip De Jager, MD, PhD (Columbia University Irving Medical Center)	Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. De Jager has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Puretech. Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for roche. Dr. De Jager has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. The institution of Dr. De Jager has received research support from roche. The institution of Dr. De Jager has received research support from Biogen. The institution of Dr. De Jager has received research support from puretech.
Bogachan Sahin, MD (University of Rochester Medical Center)	No disclosure on file

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