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Differential diagnosis of Alzheimer's disease using spectrochemical analysis of blood.

ABSTRACT: The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer's disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ?4 genotype (APOE ?4) information, increased to 86% when individuals carried one or two alleles of ?4, and to 72% sensitivity and 77% specificity when individuals did not carry ?4 alleles. Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson's disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.

SUBMITTER: Paraskevaidi M

PROVIDER: S-EPMC5617251 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Differential diagnosis of Alzheimer's disease using spectrochemical analysis of blood.

Paraskevaidi Maria M Morais Camilo L M CLM Lima Kássio M G KMG Snowden Julie S JS Saxon Jennifer A JA Richardson Anna M T AMT Jones Matthew M Mann David M A DMA Allsop David D Martin-Hirsch Pierre L PL Martin Francis L FL

Proceedings of the National Academy of Sciences of the United States of America 20170905 38

The progressive aging of the world's population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometr ...[more]

PMID: 28874525

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Project description:BackgroundWith demographic shifts toward older populations, the number of people with dementia is steadily increasing. Alzheimer's disease (AD) is the most common cause of dementia, and no curative treatment is available. The current best strategy is to delay disease progression and to practice early intervention to reduce the number of patients that ultimately develop AD. Therefore, promising novel biomarkers for early diagnosis are urgently required.MethodsTo identify blood-based biomarkers for early diagnosis of AD, we performed RNA sequencing (RNA-seq) analysis of 610 blood samples, representing 271 patients with AD, 91 cognitively normal (CN) adults, and 248 subjects with mild cognitive impairment (MCI). We first estimated cell-type proportions among AD, MCI, and CN samples from the bulk RNA-seq data using CIBERSORT and then examined the differentially expressed genes (DEGs) between AD and CN samples. To gain further insight into the biological functions of the DEGs, we performed gene set enrichment analysis (GSEA) and network-based meta-analysis.ResultsIn the cell-type distribution analysis, we found a significant association between the proportion of neutrophils and AD prognosis at a false discovery rate (FDR) < 0.05. Furthermore, a similar trend emerged in the results of routine blood tests from a large number of samples (n = 3,099: AD, 1,605; MCI, 994; CN, 500). In addition, GSEA and network-based meta-analysis based on DEGs between AD and CN samples revealed functional modules and important hub genes associated with the pathogenesis of AD. The risk prediction model constructed by using the proportion of neutrophils and the most important hub genes (EEF2 and RPL7) achieved a high AUC of 0.878 in a validation cohort; when further applied to a prospective cohort, the model achieved a high accuracy of 0.727.ConclusionsOur model was demonstrated to be effective in prospective AD risk prediction. These findings indicate the discovery of potential biomarkers for early diagnosis of AD, and their further improvement may lead to future practical clinical use.

Project description:BackgroundPhase-contrast magnetic resonance imaging (PC-MRI) enables quantification of cerebrospinal fluid (CSF) flow and total cerebral blood (tCBF) flow and may be of value for the etiological diagnosis of neurodegenerative diseases. This investigation aimed to study CSF flow and intracerebral vascular flow in patients with Alzheimer's disease (AD) and patients with amnesic mild cognitive impairment (a-MCI) and to compare the results with patients with idiopathic normal pressure hydrocephalus (NPH) and with healthy elderly volunteers (HEV).MethodsTen a-MCI and 9 mild AD patients were identified in a comprehensive neurological and neuropsychological assessment. They underwent brain MRI; PC-MRI pulse sequence was performed with the following parameters: two views per segment; flip angle: 25° for vascular flow and 20° for CSF flow; field-of-view (FOV): 14 × 14 mm²; matrix: 256 × 128; slice thickness: 5 mm; with one excitation for exams on the 3 T machine, and 2 excitations for the 1.5 T machine exams. Velocity (encoding) sensitization was set to 80 cm/s for the vessels at the cervical level, 10 or 20 cm/s for the aqueduct and 5 cm/s for the cervical subarachnoid space (SAS). Dynamic flow images were analyzed with in-house processing software. The patients' results were compared with those obtained for HEVs (n = 12), and for NPH patients (n = 13), using multivariate analysis.ResultsArterial tCBF and the calculated pulsatility index were significantly greater in a-MCI patients than in HEVs. In contrast, vascular parameters were lower in NPH patients. Cervical CSF flow analysis yielded similar values for all four populations. Aqueductal CSF stroke volumes (in μl per cardiac cycle) were similar in HEVs (34 ± 17) and AD patients (39 ± 18). In contrast, the aqueductal CSF was hyperdynamic in a-MCI patients (73 ± 33) and even more so in NPH patients (167 ± 89).ConclusionOur preliminary data show that a-MCI patients present with high systolic arterial peak flows, which are associated with higher mean total cerebral arterial flows. Aqueductal CSF oscillations are within normal range in AD and higher than normal in NPH. This study provides an original dynamic vision of cerebral neurodegenerative diseases, consistent with the vascular theory for AD, and supporting primary flow disturbances different from those observed in NPH.

Dataset Information

Differential diagnosis of Alzheimer's disease using spectrochemical analysis of blood.

Publications

Differential diagnosis of Alzheimer's disease using spectrochemical analysis of blood.

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