Dataset Information

Cerebrospinal fluid A?42 levels and APP processing pathway genes in Parkinson's disease.

ABSTRACT: Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (A?), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF A?42 levels in Parkinson's disease (PD).Parkinson's disease (n?=?86) and control (n?=?161) DNA were genotyped for 19 regulatory region tagging single-nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ?4 status.Significant correlation with CSF A?42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF A?42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344).In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF A?42 levels in APOE ?4 noncarriers. Further hypotheses generated include that decreased CSF A?42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society.

SUBMITTER: Bekris LM

PROVIDER: S-EPMC4478197 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.

Bekris Lynn M LM Tsuang Debby W DW Peskind Elaine R ER Yu Chang E CE Montine Thomas J TJ Zhang Jing J Zabetian Cyrus P CP Leverenz James B JB

Movement disorders : official journal of the Movement Disorder Society 20150324 7

<h4>Background</h4>Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).<h4>Methods</h4>Parkinson's disease (n = 86) and control (n = 161) DNA ...[more]

PMID: 25808939

Similar Datasets

Project description:Background and aimToxic oligomeric α-synuclein (αS; O-αS) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of αS, O-αS, total and phosphorylated tau, and amyloid β 1-42 (Aβ1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naïve patients with PD.MethodsTwenty-seven drug-naïve patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total αS, O-αS, Aβ1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated.ResultsCSF levels of αS were negatively correlated with UPDRS part III (motor score) (p < 0.05) and bradykinesia (p < 0.01), and positively correlated with COGNISTAT subtest of judgement (p < 0.01) and CSF levels of Aβ1-42 (p < 0.001), total tau (p < 0.001) and P-tau181p (p < 0.01). Lower CSF levels of Aβ1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-αS showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins.ConclusionCSF levels of αS are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naïve PD patients. These correlations suggest a central role for interaction and aggregation of αS with Aβ1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-αS has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

Dataset Information

Cerebrospinal fluid A?42 levels and APP processing pathway genes in Parkinson's disease.

Publications

Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets