Transcriptome-wide expression analysis of pooled brain samples of patients with Alzheimer's disease compared to controls
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ABSTRACT: Brain tissue of 3 patients with Alzheimer's disease (AD) and 3 healthy controls dying without any history of neurological or psychiatric illness was used. The diagnosis of AD was made on the basis of both clinical and neuropathological evidence according to the criteria of the International Working Group (IWG) for New Research Criteria for the diagnosis of AD in the revision of 2014 (IWG-2),16 the NIA-AA diagnostic criteria in the revision of 201117 and the NIA-AA guidelines for the neuropathological assessment of AD. Only cases with typical AD according to IWG-2 criteria were included. Transcriptome-wide expression of AD and healthy control samples was assessed with Affymetrix Human Whole Genome Tiling Array 1.0 Set.
Project description:Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration as a result of abnormal neuronal loss. To elucidate the molecular systems associated with AD, we characterized the gene expression changes associated with multiple clinical and neuropathological traits in 1,053 postmortem brain samples across 19 brain regions from 125 persons dying with varying severities of dementia and variable AD-neuropathology severities. 125 human brains were accessed from the Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB). This brain resource was assembled after applying stringent inclusion/exclusion criteria and represents the full spectrum of clinical and neuropathological disease severity in the absence of discernable non-AD neuropathology. RNA samples from 19 brain regions isolated from the 125 MSBB specimens were collected and profiled using Affymetrix Genechip microarrays. There were 50 to 60 subjects per brain region with varying degrees of AD pathological abnormalities.
Project description:To identify the potential biomarkers of Alzheimer's disease (AD) based on circulating microRNAs (miRNAs), we developed a new approach using feature selection and linear mixed model. The miRNA sequencing data of 105 plasma and 112 serum samples from 112 subjects including 28 AD cases, 63 mild cognitive impairment (MCI), and 21 controls were used to identify cerebrospinal fluid biomarkers associated miRNAs. The potential of these miRNAs as biomarkers of AD or MCI was researched and validated via both internal and external dataset. Patient classification was effectuated in compliance with the NIA-AA criteria for “MCI due to AD” and “Dementia due to AD”.
Project description:Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration as a result of abnormal neuronal loss. To elucidate the molecular systems associated with AD, we characterized the gene expression changes associated with multiple clinical and neuropathological traits in 1,053 postmortem brain samples across 19 brain regions from 125 persons dying with varying severities of dementia and variable AD-neuropathology severities.
Project description:The aim of the study was to identify genes which are differentially expressed in the blood of dogs with canine atopic dermatitis (AD) before and after 6 months of allergen-specific immunotherapy (ASIT) in comparison to healthy control dogs. Diagnosis of AD was based on compatible history and clinical signs determined using Willemse and Prélaud diagnostic criteria, completed by Favrot criteria as follows: pruritus sine material, indoor lifestyle and the exclusion of other causes of pruritus ongoing for at least one year. Clinical diagnosis of atopic dermatitis was confirmed by serological allergy testing (IDEXX allergic panel test) and intradermal skin testing (Artuvetrin test set, Netherlands). In order to avoid the role of food antigens as a cause of the skin condition elimination diet was used for 6–8 weeks. No anti-inflammatory drugs were given for at least 3 weeks prior examination with serological test, intradermal test and blood collection. All dogs, which were classified to the investigated group had positive reactions in serological allergy testing and intradermal skin testing. Subsequently, subcutaneous allergen-specific immunotherapy was applied. Allergen extracts were prepared on the basis of the results of intradermal tests by the Artuvetrin company and were administered subcutaneously in increasing concentrations during 6 months according to the manufacturer's recommendations. Aside from gene regulation, this experiment also examined the participation of individual lymphocyte subpopulations (like: B, T, Th, Tc, Treg) and the level of interleukins in the blood of AD dogs before and after therapy.
Project description:The aim of the study was to identify genes which are differentially expressed in the blood of dogs with canine atopic dermatitis (AD) in comparison to healthy control dogs. Diagnosis of AD was based on compatible history and clinical signs determined using Willemse and Prélaud diagnostic criteria, completed by Favrot criteria as follows: pruritus sine material, indoor lifestyle and the exclusion of other causes of pruritus ongoing for at least one year. Clinical diagnosis of atopic dermatitis was confirmed by serological allergy testing (IDEXX allergic panel test) and intradermal skin testing (Artuvetrin test set, Netherlands). In order to avoid the role of food antigens as a cause of the skin condition elimination diets was used for 6–8 weeks. No anti-inflammatory drugs were given for at least 3 weeks prior examination with serological test, intradermal test and blood collection. All dogs, which were classified to the investigated group had positive reactions in serological allergy testing and intradermal skin testing.
Project description:Cervical mucus was collected from 86 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). 76 candidates of miRNAs were selected according to criteria such as absolute value of the signal intensity included more than 20 and the ratio of the SCC/normal or AD/normal included more than four.
Project description:Aging is often characterized by a progressive loss of cognitive abilities due to the onset of different forms of dementia. Among these, Alzheimer’s Disease (AD) and dementia with Lewy bodies (LBD) are the most widespread ones. However, little is known about the common aspects between these conditions and how these aspects can be linked to aging itself. With this work, we aim to identify a molecular fil rouge that could link aging and different dementias in order to possibly highlight strategic targets for novel therapeutical approaches. A whole transcriptome analysis and a Gene Set Enrichment Analysis (GSEA) have been carried out on brain samples from hippocampus (HI), temporal and parietal cortex (TC, PC), cingulate cortex (CG), and substantia nigra (SN) from the Abbiategrasso Brain Bank (ABB) of subjects with a neuropathological diagnosis of AD and LBD (6 per pathology) and 3 age-matched controls with no dementia (CTRLs). Clinical and neuropsychological profile were obtained through serial evaluations, made at the baseline and in the following years. According to the ABB protocol, the neuropathological diagnosis was based on a complete histological characterization, including all the main proteinopathies and vascular scoring. Transcriptomic results showed some major differences in the number of differentially expressed genes (DEGs) between the two pathologies and in particular that AD brains gene expression is more affected compared to LBD’s one (DEGsAD=3156; DEGsLBD=278). Furthermore, the GSEA showed that in AD it is possible to cluster the analysed regions by biological processes (HI and TC: DEGs primarily related to synaptic transmission; PC, CG and SN: DEGs primarily related to proper protein folding and inflammation) while in LBD there is only a strong and peculiar involvement of SN (DEGs primarily related to proper protein folding and inflammation) and PC (DEGs primarily related to myelination and glial system activation). AD and LBD are different forms of dementia characterized by a definite time and severity-related pattern. Therefore, it is possible to draw a molecular map of pathology spreading in the brain that could unveil unexplored roads and possible shortcuts leading to a better understanding of AD and LBD pathogenesis. This could help to discover novel biological targets in order to develop effective and well-timed therapeutical approaches.
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from 2 chronic nonunion patients collected perioperatively (pre/post revision surgery) and at 3 months post revision follow up for comparison to Acutely injured subjects and Healthy volunteer cohorts analyzed separately. We used microarrays to do a global comparison between 2 chronic nonunion patients collected perioperatively (pre/post revision surgery) and at 3 months post revision follow up.
Project description:The specific genes that distinguish normal fracture healing from abnormal healing or nonunion in humans are unknown. This study was an exploratory investigation of peripheral blood from 2 chronic nonunion patients collected perioperatively (pre/post revision surgery) and at 3 months post revision follow up for comparison to Acutely injured subjects and Healthy volunteer cohorts analyzed separately. We used microarrays to do a global comparison between 2 chronic nonunion patients collected perioperatively (pre/post revision surgery) and at 3 months post revision follow up.
Project description:In this project we performed a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via label-free shotgun proteomics. We enrolled adult (≥18 years old) patients with sepsis from community-acquired infections, diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria. Blood samples were obtained within the first 72 hours from the diagnosis of sepsis (sepsis phase) and on de day before ICU discharge (recovery phase). The Control group consisted of age matched healthy volunteers. We excluded subjects with AIDS, advanced cancer, hematological diseases, and pregnancy.