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The clinical significance of plasma clusterin and A? in the longitudinal follow-up of patients with Alzheimer's disease.

ABSTRACT: Clusterin and beta-amyloid (A?) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and A? in AD progression remains controversial.We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. All participants were evaluated at baseline with a clinical assessment, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were evaluated annually with the MMSE and Neuropsychiatric Inventory (NPI) scale during the 2-year follow-up period. The levels of plasma clusterin, A?1-40, and A?1-42 at baseline were analyzed to study the longitudinal changes in the patient scores on the MMSE and NPI during the follow-up period.Patients in the highest tertile of plasma clusterin levels showed significantly lower MMSE scores than those in the lowest tertile (p?=?0.04). After adjustment for multiple covariates using the generalized estimating equation analysis, there was a significant decrease in the MMSE scores over the 2-year follow-up period among AD patients in the highest tertile of plasma clusterin levels compared with those in the lowest tertile (-2.09, 95% confidence interval (CI)?=?-3.67 to -0.51, p?=?0.01). In apolipoprotein E (ApoE)4-positive AD patients, baseline measurements of the ratio of plasma A?1-42/A?1-40 in the highest tertile predicted an increase in NPI agitation/aggression scores over the 2-year follow-up period (6.06, 95% CI?=?1.20-10.62, p?=?0.02).Plasma clusterin could serve as a biomarker for the severity of cognitive decline. Plasma A? in ApoE4-positive AD could predict long-term agitation/aggression symptoms.

SUBMITTER: Hsu JL

PROVIDER: S-EPMC5701424 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The clinical significance of plasma clusterin and Aβ in the longitudinal follow-up of patients with Alzheimer's disease.

Hsu Jung-Lung JL Lee Wei-Ju WJ Liao Yi-Chu YC Wang Shuu-Jiun SJ Fuh Jong-Ling JL

Alzheimer's research & therapy 20171123 1

<h4>Background</h4>Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial.<h4>Methods</h4>We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. All participants were evaluated at baseline with a clinical assessment, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were evaluated annually ...[more]

PMID: 29169407

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Project description:Although plasma globotriaosylsphingosine (lyso-Gb3) is a promising biomarker of Fabry disease (FD), few studies have assessed the impact of lyso-Gb3 in patients with FD. A total of 38 patients diagnosed with FD at Ruijin Hospital between January 2012 and December 2014 were recruited in the current study. An additional 120 unrelated healthy individuals were selected as healthy controls. A simplified liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was performed to determine lyso-Gb3 levels in plasma. Protein precipitation and glycolipid extraction were conducted using acetone/methanol. Clinical performance, including diagnostic value and disease surveillance, were compared between plasma lyso-Gb3 levels and ?-galactosidase A (?-gal A) enzyme activity. The overall coefficient of variation values between inter- and intra-days varied between 2.8 and 18.9% and linearity correlation coefficients were ?0.99 for all assays. Therefore, the effectiveness of the LC-MS/MS method was validated. Furthermore, a cut-off value of 0.81 ng/ml plasma lyso-Gb3 was able to separate patients with FD from healthy individuals. The sensitivity of this cut-off was 94.7% and the specificity was 100%. Compared with ?-gal A enzyme activity, the diagnostic rate of patients assessed using plasma lyso-Gb3 levels was similar; however, there was a tighter correlation between plasma lyso-Gb3 levels and the mainz severity score index score in male patients (r=0.711 vs. r=-0.687). The sensitivity of plasma lyso-Gb3 in diagnosing female patients with FD was higher than ?-gal A enzyme activity (82.4 vs. 23.5%). To the best of our knowledge, the present study is the first to report the effectiveness of plasma lyso-Gb3 levels in diagnosing Chinese patients with FD. Using ?-gal A activity as a reference, the results of current study indicated that plasma lyso-Gb3 levels are more useful at diagnosing female patients with FD. Furthermore, plasma lyso-Gb3 levels are more suitable at determining overall disease severity in male patients.

Dataset Information

The clinical significance of plasma clusterin and A? in the longitudinal follow-up of patients with Alzheimer's disease.

Publications

The clinical significance of plasma clusterin and Aβ in the longitudinal follow-up of patients with Alzheimer's disease.

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