Viewing zone enlargement method for holographic displays based on the slanted pixel arrangement on a spatial light modulator.

This study proposes a method for enlarging the viewing zone of holographic displays using the slanted arrangement of pixels on a spatial light modulator (SLM). The pixel arrangement equivalently reduces the horizontal pixel pitch, which enlarges the horizontal viewing zone of displays. Computer-generated holograms (CGHs) were calculated using an asymmetric band-limit filter corresponding to the asymmetric bandwidth of the SLM with slanted pixels. The proposed methods were evaluated through an optical reconstruction experiment using static holograms with a pixel size of 1×1µm, fabricated via electron-beam lithography. The enlarged horizontal viewing zone angle was found to be 41.6°.

Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer's Disease Neuroimaging Initiative cohort.

Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10-8 and 4.3 × 10-7). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD.

Relationship between olfactory and gustatory functions: The Iwaki health promotion project 2019.

OBJECTIVE: Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population. METHODS: We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating. RESULTS: Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women. CONCLUSION: These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.

Predicting positron emission tomography brain amyloid positivity using interpretable machine learning models with wearable sensor data and lifestyle factors.

BACKGROUND: Developing a screening method for identifying individuals at higher risk of elevated brain amyloid burden is important to reduce costs and burden to patients in clinical trials on Alzheimer's disease or the clinical setting. We developed machine learning models using objectively measured lifestyle factors to predict elevated brain amyloid burden on positron emission tomography. METHODS: Our prospective cohort study of non-demented, community-dwelling older adults aged ≥ 65 years was conducted from August 2015 to September 2019 in Usuki, Oita Prefecture, Japan. One hundred and twenty-two individuals with mild cognitive impairment or subjective memory complaints (54 men and 68 women, median age: 75.50 years) wore wearable sensors and completed self-reported questionnaires, cognitive test, and positron emission tomography imaging at baseline. Moreover, 99 individuals in the second year and 61 individuals in the third year were followed up. In total, 282 eligible records with valid wearable sensors, cognitive test results, and amyloid imaging and data on demographic characteristics, living environments, and health behaviors were used in the machine learning models. Amyloid positivity was defined as a standardized uptake value ratio of ≥ 1.4. Models were constructed using kernel support vector machine, Elastic Net, and logistic regression for predicting amyloid positivity. The mean score among 10 times fivefold cross-validation repeats was utilized for evaluation. RESULTS: In Elastic Net, the mean area under the receiver operating characteristic curve of the model using objectively measured lifestyle factors alone was 0.70, whereas that of the models using wearable sensors in combination with demographic characteristics and health and life environment questionnaires was 0.79. Moreover, 22 variables were common to all machine learning models. CONCLUSION: Our machine learning models are useful for predicting elevated brain amyloid burden using readily-available and noninvasive variables without the need to visit a hospital. TRIAL REGISTRATION: This prospective study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of Oita University Hospital (UMIN000017442). A written informed consent was obtained from all participants. This research was performed based on the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.

Nationwide Database Analysis of Risk Factors Associated with Decreased Activities of Daily Living in Patients with Alzheimer's Disease.

BACKGROUND: Preserving activities of daily living (ADL) is the key issue for Alzheimer's disease (AD) patients and their caregivers. OBJECTIVE: To clarify the ADL level of AD patients at diagnosis and the risk factors associated with decreased ADL during long-term care (≤3 years). METHODS: Medical records of AD patients in a Japanese health insurance claims database were analyzed retrospectively to determine ADL using the Barthel Index (BI) and identify the risk factors associated with decreased ADL. RESULTS: A total of 16,799 AD patients (mean age at diagnosis: 83.6 years, 61.5% female) were analyzed. Female patients were older (84.6 versus 81.9 years; p < 0.001) and had lower BI (46.8 versus 57.6; p < 0.001) and body mass index (BMI) (21.0 versus 21.7 kg/m2; p < 0.001) than male patients at diagnosis. Disability (BI≤60) increased at age≥80 years and was significantly higher in females. Complete disability was most frequent for bathing and grooming. Risk factors for decreased ADL were determined separately by sex through comparing the ADL-preserved and ADL-decreased groups using propensity score matching by age and BI and multivariable logistic regression analysis. In males, decreased ADL was significantly associated with BMI < 21.5 kg/m2, stroke, and hip fracture, and inversely associated with hyperlipidemia. In females, decreased ADL was significantly associated with BMI < 21.5 kg/m2 and vertebral and hip fractures, and inversely associated with lower back pain. CONCLUSION: AD patients with low BMI, stroke, and fractures had increased risks of decreased ADL; such patients should be identified early and managed appropriately, including rehabilitation to preserve ADL.

Magneto-optical spatial light modulator driven by current-induced domain wall motion for holographic display applications.

We have developed a magneto-optical spatial light modulator (MO-SLM) with a 10 k × 5 k pixel layout and with a pixel pitch horizontally of 1 µm and vertically of 4 µm. An MO-SLM device pixel has a magnetic nanowire made of Gd-Fe magneto-optical material whose magnetization was reversed by current-induced magnetic domain wall motion. We successfully demonstrated the reconstruction of holographic images, showing large viewing zone angles as wide as 30 degrees and visualizing different depths of the objects. These characteristics are unique to holographic images, providing physiological depth cues which may play a vital role in three-dimensional (3D) perception.

Image quality assessment procedure for holographic displays based on exact numerical reconstruction of computer-generated holograms.

We proposed a technique for the computer-based reconstruction of computer-generated holograms and evaluation of the reconstructed 3D image quality. The proposed method mimics how the eye's lens works, thus allowing for viewing position and eye focus adjustments. The angular resolution of the eye was used to output reconstructed images with the requisite resolution, and a reference object was used to normalize the images. Such data processing enables the numerical analysis of image quality. By comparing the reconstructed images with the original image with incoherent illumination, the image quality was quantitatively evaluated.

Nationwide database analysis of insomnia, depression, and sleeping pill prescriptions in hepatocellular carcinoma patients.

OBJECTIVE: To clarify the status of insomnia and depression and the prescription of sleeping pills in hepatocellular carcinoma (HCC) patients before and after HCC diagnosis and treatment. METHODS: Patients' data from a Japanese health insurance claims database were analyzed retrospectively to determine the incidence of insomnia and depression and their association with sleeping pill prescriptions during the 6 months before and after HCC diagnosis and treatment. RESULTS: A total of 9,109 HCC patients (median age at diagnosis = 71.5 years, 68.1% male) were analyzed. The incidences of insomnia and depression increased significantly after HCC diagnosis. Insomnia was reported in 15.0% of patients before diagnosis, and it increased to 27.6% after diagnosis. Similarly, depression was reported in 6.3% and 11.3% before and after diagnosis, respectively. The incidences of insomnia and depression before diagnosis were higher in patients with concomitant liver diseases including hepatitis, cirrhosis, and hepatic encephalopathy. However, the rate of sleeping pill prescription was significantly lower in patients with concomitant liver diseases after diagnosis. The incidence of fracture was higher in insomnia or depression patients than others and in patients treated with sleeping pills than without before and after diagnosis. CONCLUSIONS: HCC patients had increased risks of insomnia and depression after diagnosis. The high risk of fracture in HCC patients with insomnia and depression and treated with sleeping pills suggests that it is difficult to optimize the management of HCC patients, especially those with concomitant liver diseases.

A deep learning algorithm for sleep stage scoring in mice based on a multimodal network with fine-tuning technique.

Sleep stage scoring is important to determine sleep structure in preclinical and clinical research. The aim of this study was to develop an automatic sleep stage classification system for mice with a new deep neural network algorithm. For the purpose of base feature extraction, wake-sleep and rapid eye movement (REM) and non- rapid eye movement (NREM) models were developed by extracting defining features from mouse-derived electromyogram (EMG) and electroencephalogram (EEG) signals, respectively. The wake-sleep model and REM-NREM sleep model were integrated into three different algorithms including a rule-based integration approach, an ensemble stacking approach, and a multimodal with fine-tuning approach. The deep learning algorithm assessing sleep stages in animal experiments by the multimodal with fine-tuning approach showed high potential for increasing accuracy in sleep stage scoring in mice and promoting sleep research.

Real-world database analysis of the characteristics and treatment patterns of patients with endometrial cancer in Japan.

OBJECTIVE: The aim was to identify the characteristics and treatment patterns of early and advanced stage endometrial cancer patients using real-world data. METHODS: Patients' data extracted from a Japanese health insurance claims database were analyzed. RESULTS: Of the 12,449 endometrial cancer patients, 74.4% were in stage I, 5.1% in stage II, 12.0% in stage III, and 8.4% in stage IV. Their median age was 60.5 years, higher in advanced stages (III/IV) than in early stages (I/II). Overall, 11,055 patients (88.8%) underwent surgery, and 4977 patients (40.0%) received post-surgery treatment, including chemotherapy (4441: 35.7%), chemoradiation therapy (379: 3.0%), and radiation therapy (157 patients: 1.3%); 1394 patients (11.2%) were not treated by surgery, and 742 patients (6.0%) received other treatment, with chemotherapy (548: 4.4%), radiation therapy (105: 0.8%), and chemoradiation therapy (89: 0.7%). The rate of patients undergoing surgery decreased, and that receiving chemotherapy increased significantly as cancer stage progressed. Paclitaxel/carboplatin was the most frequent first-line regimen (85.4% of patients), whereas various combination and monotherapy regimens were used as second- and third-line regimens. The most frequent second-line monotherapy was paclitaxel. The rate of monotherapy increased as the treatment line progressed (first-line 3.5%, second-line 22.0%, and third-line 36.4%). CONCLUSIONS: The characteristics and treatment patterns of endometrial cancer patients differed between early and advanced stages, as did the chemotherapy regimens among first-, second-, and third-lines. Since various regimens were used for second- and third-line chemotherapies, development of appropriate second- and third-line chemotherapy regimens is warranted. A real-world analysis of cancer patients using a nationwide claims database may be a valuable approach to identifying unmet medical needs.

Identification of prognostic factors to predict cognitive decline of patients with early Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative study.

INTRODUCTION: The objective of this study was to determine the factors including neuropsychological test performances and cerebrospinal fluid (CSF) biomarkers which can predict disease progression of early Alzheimer's disease (AD) in a Japanese population. METHODS: The group classification on early AD population in both Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and North American ADNI (NA-ADNI) was performed using the inclusion criteria including brain amyloid positivity on positron emission tomography or CSF. Participants with early AD from each cohort were stratified into two groups based on a cutoff 1.0 of Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) change at month 24 (m24): participants in "progress group" have CDR-SB change ≥ 1.0 and participants in "stable group" have CDR-SB change < 1.0. Then, we performed identification of prognostic factors from baseline items including neuropsychological scores (Assessment Scale-Cognitive Subscale[ADAS-cog 13], Mini-Mental State Examination (MMSE), CDR, FAQ, and Geriatric Depression Scale ), CSF markers (t-tau, p-tau, and beta-amyloid 1-42), vital signs (body weight, pulse rate, etc.,), by using two statistical approaches, Welch's t-test and simple linear regression by ordinary least squares. Comparisons between participants with J-ADNI and participants with NA-ADNI were also performed. RESULTS: Trends of CDR-SB changes were very similar between J-ADNI and NA-ADNI early AD population enrolled in this study. Baseline levels of CSF t-tau, p-tau, Mini-Mental State Examination, FAQ, and ADAS-cog13 were identified as prognostic factors in both J-ADNI and NA-ADNI. Based on a detailed subscale analysis on ADAS-cog13, four subscales (Q1: word recall, Q3: construction, Q4: delayed word recall, and Q8: word recognition) were identified as prognostic factors in both J-ADNI and NA-ADNI. DISCUSSION: Characterizing population with early AD can provide benefits for promoting efficiency in conducting AD clinical trials for disease-modifying treatments. Thus, implementing these prognostic factors into clinical trials may be potentially a good method to enrich participants with early AD who are suitable for evaluating treatment effects.

Database analysis of patients with hepatocellular carcinoma and treatment flow in early and advanced stages.

Despite recent developments in treatment modalities and diagnosis, the prognosis of advanced hepatocellular carcinoma (HCC) remains unsatisfactory. To gain insight into treatment decisions for HCC patients, their characteristics and treatment flow in the early and advanced stages were examined. HCC patients' characteristics and treatment flow were retrospectively analyzed using the Japanese medical claims database. The 8999 patients' mean age at HCC diagnosis was 71.1 years, with no difference between early (Stage I/II) and advanced (Stage III/IV) stages. The mean observation period was 26.2 months, shorter in advanced than in early stages. HCV hepatitis was reported in 52.0% of HCC patients, with concomitant hypertension in 53.4%, type 2 diabetes in 45.8%, cirrhosis in 39.3%, and hyperlipidemia in 15.5%. The rates of HCV hepatitis, hypertension, and hyperlipidemia decreased with stage progression. Analysis of treatment flow showed that, at all disease stages, transcatheter arterial chemoembolization (TACE) was the most common first to fourth-line treatment. Epirubicin was the most frequently (44.1%) used chemotherapeutic agent for first-line TACE, followed by miriplatin (23.6%) and cisplatin (12.3%). With stage progression, cisplatin use increased. Sorafenib was used concomitantly for first-line TACE in 3.2% of patients, and its use increased significantly in advanced stages. Clear differences in baseline characteristics and treatment flow between early and advanced stages were identified. Continuous analysis of the database with longer follow-up may provide useful information about treatment selection and prediction of outcome such as survival.

Optical and Magneto-Optical Properties of Gd22Fe78 Thin Films in the Photon Energy Range From 1.5 to 5.5 eV.

Optical and magneto-optical properties of amorphous Gd22Fe78 (GdFe) thin films prepared by direct current (DC) sputtering on thermally oxidized substrates were characterized by the combination of spectroscopic ellipsometry and magneto-optical spectroscopy in the photon energy range from 1.5 to 5.5 eV. Thin SiNx and Ru coatings were used to prevent the GdFe surface oxidation and contamination. Using advanced theoretical models spectral dependence of the complete permittivity tensor and spectral dependence of the absorption coefficient were deduced from experimental data. No significant changes in the optical properties upon different coatings were observed, indicating reliability of used analysis.

GlycanAnalysis Plug-in: a database search tool for N-glycan structures using mass spectrometry.

UNLABELLED: Tandem mass spectrometry (MS/MS or MS(n)) is a potent technique for characterizing N-glycan structures. GlycanAnalysis searches a glycan database to support the identification of glycan structures from MS/MS spectra. It also calculates diagnostic ions of glycan structures registered in a glycan database (GlycomeDB or KEGG GLYCAN) and searches for MS/MS spectra of N-glycans that match diagnostic ions to determine the structures. This program functions as a plug-in for Mass++, a freeware mass spectrum visualization and analysis program. AVAILABILITY AND IMPLEMENTATION: The executable files of Mass++ are available for free at http://www.first-ms3d.jp/english/. The GlycanAnalysis plug-in is included in the standard package of Mass++ for Windows. CONTACT: k-morimt@shimadzu.co.jp or nishikaz@shimadzu.co.jp or acyshzw@shimadzu.co.jp SUPPLEMENTARY INFORMATION: Supplementary material are available at Bioinformatics online.

Reduced plasma desmosterol-to-cholesterol ratio and longitudinal cognitive decline in Alzheimer's disease.

BACKGROUND: We here examined whether plasma desmosterol-to-cholesterol ratio (DES/CHO) is decreased in patients with Alzheimer's disease (AD) and investigated the association between plasma DES/CHO and longitudinal cognitive decline. METHODS: Plasma DES/CHO of AD patients and age-matched controls in a Japanese cross-sectional cohort was determined. Plasma DES/CHO at baseline and follow-up visits was assessed in relation to cognitive decline in Japanese and Swedish longitudinal cohorts. RESULTS: Plasma DES/CHO was significantly reduced in Japanese AD patients and significantly correlated with Mini-Mental State Examination (MMSE) score. The longitudinal analysis revealed that plasma DES/CHO in AD patients shows a significant decrease at follow-up intervals. The decline in plasma DES/CHO is larger in the AD group with rapid progression than in that with slow progression. The changes in plasma DES/CHO significantly correlated with changes in the MMSE score. CONCLUSION: Plasma DES/CHO is decreased in AD patients and may serve as a longitudinal surrogate marker associated with cognitive decline.

A simple peak detection and label-free quantitation algorithm for chromatography-mass spectrometry.

BACKGROUND: Label-free quantitation of mass spectrometric data is one of the simplest and least expensive methods for differential expression profiling of proteins and metabolites. The need for high accuracy and performance computational label-free quantitation methods is still high in the biomarker and drug discovery research field. However, recent most advanced types of LC-MS generate huge amounts of analytical data with high scan speed, high accuracy and resolution, which is often impossible to interpret manually. Moreover, there are still issues to be improved for recent label-free methods, such as how to reduce false positive/negatives of the candidate peaks, how to expand scalability and how to enhance and automate data processing. AB3D (A simple label-free quantitation algorithm for Biomarker Discovery in Diagnostics and Drug discovery using LC-MS) has addressed these issues and has the capability to perform label-free quantitation using MS1 for proteomics study. RESULTS: We developed an algorithm called AB3D, a label free peak detection and quantitative algorithm using MS1 spectral data. To test our algorithm, practical applications of AB3D for LC-MS data sets were evaluated using 3 datasets. Comparisons were then carried out between widely used software tools such as MZmine 2, MSight, SuperHirn, OpenMS and our algorithm AB3D, using the same LC-MS datasets. All quantitative results were confirmed manually, and we found that AB3D could properly identify and quantify known peptides with fewer false positives and false negatives compared to four other existing software tools using either the standard peptide mixture or the real complex biological samples of Bartonella quintana (strain JK31). Moreover, AB3D showed the best reliability by comparing the variability between two technical replicates using a complex peptide mixture of HeLa and BSA samples. For performance, the AB3D algorithm is about 1.2 - 15 times faster than the four other existing software tools. CONCLUSIONS: AB3D is a simple and fast algorithm for label-free quantitation using MS1 mass spectrometry data for large scale LC-MS data analysis with higher true positive and reasonable false positive rates. Furthermore, AB3D demonstrated the best reproducibility and is about 1.2- 15 times faster than those of existing 4 software tools.

Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models.

Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models. Vascular remodeling associated with improved perfusion was shown by Hoechst 33342 staining and by increased microvessel density together with decreased mean vascular areas and fewer branched vessels in tumor tissues, as determined by immunohistochemical staining for endothelial marker CD31. Quantitative RT-PCR analysis of normal host cells in the stroma of xenograft tumors showed that eribulin altered the expression of mouse (host) genes in angiogenesis signaling pathways controlling endothelial cell-pericyte interactions, and in the epithelial-mesenchymal transition pathway in the context of the tumor microenvironment. Eribulin also decreased hypoxia-associated protein expression of mouse (host) vascular endothelial growth factor by ELISA and human CA9 by immunohistochemical analysis. Prior treatment with eribulin enhanced the anti-tumor activity of capecitabine in the MDA-MB-231 xenograft model. These findings suggest that eribulin-induced remodeling of abnormal tumor vasculature leads to a more functional microenvironment that may reduce the aggressiveness of tumors due to elimination of inner tumor hypoxia. Because abnormal tumor microenvironments enhance both drug resistance and metastasis, the apparent ability of eribulin to reverse these aggressive characteristics may contribute to its clinical benefits.

Mass++: A Visualization and Analysis Tool for Mass Spectrometry.

We have developed Mass++, a plug-in style visualization and analysis tool for mass spectrometry. Its plug-in style enables users to customize it and to develop original functions. Mass++ has several kinds of plug-ins, including rich viewers and analysis methods for proteomics and metabolomics. Plug-ins for supporting vendors' raw data are currently available; hence, Mass++ can read several data formats. Mass++ is both a desktop tool and a software development platform. Original functions can be developed without editing the Mass++ source code. Here, we present this tool's capability to rapidly analyze MS data and develop functions by providing examples of label-free quantitation and implementing plug-ins or scripts. Mass++ is freely available at http://www.first-ms3d.jp/english/ .

Peptide Peak Detection for Low Resolution MALDI-TOF Mass Spectrometry.

A new peak detection method has been developed for rapid selection of peptide and its fragment ion peaks for protein identification using tandem mass spectrometry. The algorithm applies classification of peak intensities present in the defined mass range to determine the noise level. A threshold is then given to select ion peaks according to the determined noise level in each mass range. This algorithm was initially designed for the peak detection of low resolution peptide mass spectra, such as matrix-assisted laser desorption/ionization Time-of-Flight (MALDI-TOF) mass spectra. But it can also be applied to other type of mass spectra. This method has demonstrated obtaining a good rate of number of real ions to noises for even poorly fragmented peptide spectra. The effect of using peak lists generated from this method produces improved protein scores in database search results. The reliability of the protein identifications is increased by finding more peptide identifications. This software tool is freely available at the Mass++ home page (http://www.first-ms3d.jp/english/achievement/software/).

Circulating miRNA biomarkers for Alzheimer's disease.

A minimally invasive diagnostic assay for early detection of Alzheimer's disease (AD) is required to select optimal patient groups in clinical trials, monitor disease progression and response to treatment, and to better plan patient clinical care. Blood is an attractive source for biomarkers due to minimal discomfort to the patient, encouraging greater compliance in clinical trials and frequent testing. MiRNAs belong to the class of non-coding regulatory RNA molecules of ∼22 nt length and are now recognized to regulate ∼60% of all known genes through post-transcriptional gene silencing (RNAi). They have potential as useful biomarkers for clinical use because of their stability and ease of detection in many tissues, especially blood. Circulating profiles of miRNAs have been shown to discriminate different tumor types, indicate staging and progression of the disease and to be useful as prognostic markers. Recently their role in neurodegenerative diseases, both as diagnostic biomarkers as well as explaining basic disease etiology has come into focus. Here we report the discovery and validation of a unique circulating 7-miRNA signature (hsa-let-7d-5p, hsa-let-7g-5p, hsa-miR-15b-5p, hsa-miR-142-3p, hsa-miR-191-5p, hsa-miR-301a-3p and hsa-miR-545-3p) in plasma, which could distinguish AD patients from normal controls (NC) with >95% accuracy (AUC of 0.953). There was a >2 fold difference for all signature miRNAs between the AD and NC samples, with p-values<0.05. Pathway analysis, taking into account enriched target mRNAs for these signature miRNAs was also carried out, suggesting that the disturbance of multiple enzymatic pathways including lipid metabolism could play a role in AD etiology.