RESUMEN
The relationship between reduced serum uric acid (UA) levels and Parkinson's disease (PD), particularly purine metabolic pathways, is not fully understood. Our study compared serum and cerebrospinal fluid (CSF) levels of inosine, hypoxanthine, xanthine, and UA in PD patients and healthy controls. We analyzed 132 samples (serum, 45 PD, and 29 age- and sex-matched healthy controls; CSF, 39 PD, and 19 age- and sex-matched healthy controls) using liquid chromatography-tandem mass spectrometry. Results showed significantly lower serum and CSF UA levels in PD patients than in controls (p < 0.0001; effect size r = 0.5007 in serum, p = 0.0046; r = 0.3720 in CSF). Decreased serum hypoxanthine levels were observed (p = 0.0002; r = 0.4338) in PD patients compared to controls with decreased CSF inosine and hypoxanthine levels (p < 0.0001, r = 0.5396: p = 0.0276, r = 0.2893). A general linear model analysis indicated that the reduced UA levels were mainly due to external factors such as sex and weight in serum and age and weight in CSF unrelated to the purine metabolic pathway. Our findings highlight that decreased UA levels in PD are influenced by factors beyond purine metabolism, including external factors such as sex, weight, and age, emphasizing the need for further research into the underlying mechanisms and potential therapeutic approaches.
RESUMEN
BACKGROUND: Parkinson's disease (PD) is associated with cognitive decline through multiple mechanisms, including Alzheimer's disease (AD) pathology and cortical Lewy body involvement. However, its underlying mechanisms remain unclear. Recently, AD-related plasma biomarkers have emerged as potential tools for predicting abnormal pathological protein accumulation. We aimed to investigate the association between AD-related plasma biomarkers and cognitive decline in PD patients. METHODS: Plasma biomarkers were measured in 70 PD patients (49 with nondemented Parkinson's disease (PDND) and 21 with Parkinson's disease dementia (PDD)) and 38 healthy controls (HCs) using a single-molecule array. The study evaluated (1) the correlation between plasma biomarkers and clinical parameters, (2) receiver operating characteristic curves and areas under the curve to evaluate the discrimination capacity of plasma biomarkers among groups, and (3) a generalized linear model to analyze associations with Addenbrooke's Cognitive Examination-Revised and Montreal Cognitive Assessment-Japanese version scores. RESULTS: Plasma glial fibrillary acidic protein significantly correlated with cognitive function tests, including all subdomains, with a notable increase in the PDD group compared with the HC and PDND groups, while plasma neurofilament light chain captured both cognitive decline and disease severity in the PDND and PDD groups. Plasma beta-amyloid 42/40 and pholphorylated-tau181 indicated AD pathology in the PDD group, but plasma beta-amyloid 42/40 was increased in the PDND group compared with HCs and decreased in the PDD group compared with the PDND group. CONCLUSIONS: AD-related plasma biomarkers may predict cognitive decline in PD and uncover underlying mechanisms suggesting astrocytic pathologies related to cognitive decline in PD.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Enfermedad por Cuerpos de Lewy , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/metabolismo , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Demencia/complicaciones , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Péptidos beta-Amiloides , Biomarcadores , Proteínas tau , Enfermedad por Cuerpos de Lewy/complicacionesRESUMEN
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder. We report a 59-year-old man who presented with progressive encephalomyelitis causing diplopia, bulbar palsy, severe dysautonomia, followed by stiffness and myoclonic cluster. Laboratory tests showed mild pleocytosis, with markedly elevated plasma levels of norepinephrine, epinephrine, and arginine vasopressin. Glycine-receptor antibodies were identified in both serum and CSF. Despite a poor response to methylprednisolone, immunoglobulins, and plasma exchange, α-blocker stabilized dysautonomia. Dysautonomia is presumed to be due to antibody-mediated disinhibited sympathetic hyperactivity; however, this case suggests that concomitant use of α-blocker with immunotherapy may ameliorate dysautonomia.