Dataset Information

Distinctive Pattern of Serum Elements During the Progression of Alzheimer's Disease.

ABSTRACT: Element profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer's disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the study. Manganese, iron, copper, zinc, selenium, thallium, antimony, mercury, vanadium and molybdenum changed significantly among the 4 groups. Several essential elements, such as manganese, selenium, zinc and iron tended to increase in SMC and then progressively to decrease in MCI and AD. Toxic elements show a variable behavior, since some elements tended to increase, while others tended to decrease in AD. A multivariate model, built using a panel of six essential elements (manganese, iron, copper, zinc, selenium and calcium) and their ratios, discriminated AD patients from HS with over 90% accuracy. These findings suggest that essential and toxic elements contribute to generate a distinctive signature during the progression of AD, and their monitoring in elderly might help to detect preclinical stages of AD.

SUBMITTER: Paglia G

PROVIDER: S-EPMC4783774 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Distinctive Pattern of Serum Elements During the Progression of Alzheimer's Disease.

Paglia Giuseppe G Miedico Oto O Cristofano Adriana A Vitale Michela M Angiolillo Antonella A Chiaravalle Antonio Eugenio AE Corso Gaetano G Di Costanzo Alfonso A

Scientific reports 20160309

Element profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer's disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the st ...[more]

PMID: 26957294

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Project description:Total tau (t-tau) and phosphorylated tau (p-tau) protein elevations in cerebrospinal fluid (CFS) are well-established hallmarks of Alzheimer's disease (AD), while the associations of serum t-tau and p-tau levels with AD have been inconsistent across studies. To identify more accessible non-invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age-matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild-AD group (n = 20) according to the Mini-mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t-tau, but not p-tau, was significantly higher in the mild-AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t-tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild-AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell-derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood-brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t-tau and p-tau (S202) were significantly higher in the mild-AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid ? (A?1-42) was lower in the mild-AD group compared to MCI groups (p < 0.001). During the 4-year follow-up, NEX t-tau and p-tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t-tau and p-tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression.

Project description:(1) Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that threatens the population health of older adults. However, the mechanisms of the altered metabolism involved in AD pathology are poorly understood. The aim of the study was to identify the potential biomarkers of AD and discover the metabolomic changes produced during the progression of the disease. (2) Methods: Gas chromatography-mass spectrometry (GC-MS) was used to measure the concentrations of the serum metabolites in a cohort of subjects with AD (n = 88) and a cognitively normal control (CN) group (n = 85). The patients were classified as very mild (n = 25), mild (n = 27), moderate (n = 25), and severe (n = 11). The serum metabolic profiles were analyzed using multivariate and univariate approaches. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify the potential biomarkers of AD. Biofunctional enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. (3) Results: Our results revealed considerable separation between the AD and CN groups. Six metabolites were identified as potential biomarkers of AD (AUC > 0.85), and the diagnostic model of three metabolites could predict the risk of AD with high accuracy (AUC = 0.984). The metabolic enrichment analysis revealed that carbohydrate metabolism deficiency and the disturbance of amino acid, fatty acid, and lipid metabolism were involved in AD progression. Especially, the pathway analysis highlighted that l-glutamate participated in four crucial nervous system pathways (including the GABAergic synapse, the glutamatergic synapse, retrograde endocannabinoid signaling, and the synaptic vesicle cycle). (4) Conclusions: Carbohydrate metabolism deficiency and amino acid dysregulation, fatty acid, and lipid metabolism disorders were pivotal events in AD progression. Our study may provide novel insights into the role of metabolic disorders in AD pathogenesis and identify new markers for AD diagnosis.

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Dataset Information

Distinctive Pattern of Serum Elements During the Progression of Alzheimer's Disease.

Publications

Distinctive Pattern of Serum Elements During the Progression of Alzheimer's Disease.

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