This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.0143Parkinson's Disease is a disabling disorder, causing progressive declines in motor, cognitive, and behavioral function. The underlying cause(s) of Parkinson Disease remain(s) unknown. Recently, several investigators have observed that untreated Parkinson's patients have increased serum homocysteine (Hcy) levels and that dopaminergic therapies appear to further increase them. Elevated Hcy levels have been associated with increased Parkinson's severity. Elevated Hcy levels are also commonly associated with folate deficiency. In Parkinson's patients, the reasons for elevated Hcy levels have not been identified; several small clinical trials and epidemiological studies have failed to demonstrate an effect of oral folate on Hcy levels or in reducing risk of Parkinson's, suggesting that hyperhomocysteinemia in Parkinson's may not be due to decreased dietary intake of folate. Another possibility is the presence of autoantibodies to the folate receptor. In fact, these autoantibodies increase in frequency with advancing age much the way Parkinson's does. Therefore, we hypothesize that cerebral folate deficiency due to autoantibodies may contribute to the onset and progression of Parkinson's.
Specific Aims :1. To assess the prevalence of Folate receptor autoantibodies in Parkinson's patients compared with that in age-matched controls. 2.To assess the relationship between the presence of autoantibodies and plasma Hcy levels3.To assess the relationship between Hcy and autoantibody levels and the clinical manifestations of Parkinson's. 4.To assess the relationship between Hcy and autoantibody levels and the rate of Parkinson's progression. 5.To assess the ability of orally administered L-methylfolate to lower Hcy levels and improve the signs and symptoms of Parkinson's.
|DeRosse, Pamela; Nitzburg, George C; Blair, Melanie et al. (2018) Dimensional symptom severity and global cognitive function predict subjective quality of life in patients with schizophrenia and healthy adults. Schizophr Res 195:385-390|
|Lyall, A E; Pasternak, O; Robinson, D G et al. (2018) Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning. Mol Psychiatry 23:701-707|
|Tarnawski, Laura; Reardon, Colin; Caravaca, April S et al. (2018) Adenylyl Cyclase 6 Mediates Inhibition of TNF in the Inflammatory Reflex. Front Immunol 9:2648|
|Shafritz, Keith M; Ikuta, Toshikazu; Greene, Allison et al. (2018) Frontal lobe functioning during a simple response conflict task in first-episode psychosis and its relationship to treatment response. Brain Imaging Behav :|
|Damle, Nishad R; Ikuta, Toshikazu; John, Majnu et al. (2017) Relationship among interthalamic adhesion size, thalamic anatomy and neuropsychological functions in healthy volunteers. Brain Struct Funct 222:2183-2192|
|McNamara, Robert K; Szeszko, Philip R; Smesny, Stefan et al. (2017) Polyunsaturated fatty acid biostatus, phospholipase A2 activity and brain white matter microstructure across adolescence. Neuroscience 343:423-433|
|Kafantaris, Vivian; Spritzer, Linda; Doshi, Vishal et al. (2017) Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder. Bipolar Disord 19:587-594|
|DeRosse, Pamela; Ikuta, Toshikazu; Karlsgodt, Katherine H et al. (2017) White Matter Abnormalities Associated With Subsyndromal Psychotic-Like Symptoms Predict Later Social Competence in Children and Adolescents. Schizophr Bull 43:152-159|
|Schwehm, Andrew; Robinson, Delbert G; Gallego, Juan A et al. (2016) Age and Sex Effects on White Matter Tracts in Psychosis from Adolescence through Middle Adulthood. Neuropsychopharmacology 41:2473-80|
|Cui, X; Zhang, L; Magli, A R et al. (2016) Cytoplasmic myosin-exposed apoptotic cells appear with caspase-3 activation and enhance CLL cell viability. Leukemia 30:74-85|
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