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Cerebrospinal fluid A? levels correlate with structural brain changes in Parkinson's disease.

ABSTRACT: ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (A?)38 , A?40 , A?42 , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF A? analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF A?38 and A?42 showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF A? levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.

SUBMITTER: Beyer MK

PROVIDER: S-EPMC3608817 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid Aβ levels correlate with structural brain changes in Parkinson's disease.

Beyer Mona K MK Alves Guido G Hwang Kristy S KS Babakchanian Sona S Bronnick Kolbjorn S KS Chou Yi-Yu YY Dalaker Turi O TO Kurz Martin W MW Larsen Jan P JP Somme Johanne H JH Thompson Paul M PM Tysnes Ole-Bjørn OB Apostolova Liana G LG

Movement disorders : official journal of the Movement Disorder Society 20130213 3

ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aβ)38 , Aβ40 , Aβ42 , total tau (t-tau), ...[more]

PMID: 23408705

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Project description:Background and aimToxic oligomeric ?-synuclein (?S; O-?S) 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 ?S, O-?S, total and phosphorylated tau, and amyloid ? 1-42 (A?1-42) 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 ?S, O-?S, A?1-42, 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 ?S 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 A?1-42 (p?<?0.001), total tau (p?<?0.001) and P-tau181p (p?<?0.01). Lower CSF levels of A?1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-?S showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins.ConclusionCSF levels of ?S 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 ?S with A?1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-?S has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.

Project description:ObjectiveWe analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested baseline CSF biomarkers for prediction of clinical decline in PD.MethodsAmyloid-β 1 to 42 (Aβ42 ), total tau (t-tau) and phosphorylated tau (p-tau) at the threonine 181 position were measured using the high-precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3 years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear-mixed effects models.ResultsWe found patients with PD had lower CSF t-tau (median = 157.7 pg/mL; range = 80.9-467.0); p-tau (median = 13.4 pg/mL; range = 8.0-40.1), and Aβ42 (median = 846.2 pg/mL; range = 238.8-3,707.0) than HCs at baseline (CSF t-tau median = 173.5 pg/mL; range = 82.0-580.8; p-tau median = 15.4 pg/mL; range = 8.1-73.6; and Aβ42 median = 926.5 pg/mL; range = 239.1-3,297.0; p < 0.05-0.001) and a moderate-to-strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50-0.97; p < 0.001). Of the patients with PD, 31.5% had pathologically low levels of CSF Aβ42 at baseline and these patients with PD had lower p-tau levels (median = 10.8 pg/mL; range = 8.0-32.8) compared with 27.7% of HCs with pathologically low CSF Aβ42 (CSF p-tau median = 12.8 pg/mL; range 8.2-73.6; p < 0.03). In longitudinal CSF analysis, we found patients with PD had greater decline in CSF Aβ42 (mean difference = -41.83 pg/mL; p = 0.03) and CSF p-tau (mean difference = -0.38 pg/mL; p = 0.03) at year 3 compared with HCs. Baseline CSF Aβ42 values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD.InterpretationOur data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3-year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020;88:574-587.

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Cerebrospinal fluid A? levels correlate with structural brain changes in Parkinson's disease.

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Cerebrospinal fluid Aβ levels correlate with structural brain changes in Parkinson's disease.

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