Elevations in the Levels of NF-κB and Inflammatory Chemotactic Factors in the Brains with Alzheimer's Disease - One Mechanism May Involve α3 Nicotinic Acetylcholine Receptor.

The purpose of this study was to investigate the alterations in the levels of nuclear factor κBp65 (NF-κBp65), monocyte chemoattractant protein 1 (MCP-1/CCL-2) and macrophage inflammatory protein 1α (MIP-1α/CCL-3) in relationship to the expression of α3 nicotinic acetylcholine receptor (nAChR) during the pathogenesis of Alzheimer's disease (AD). The post-mortem human brains of AD and age-matched control individuals, SH-SY5Y and U87MG cell lines exposed to β-amyloid peptide (Aβ), as well as the SH-SY5Y cells in which α3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-κBp65, MCP-1, MIP-1α and α3 nAChR. The immunohistochemistry results showed the increased immunoreactivities of NF-κBp65, MCP-1 and MIP-1α in neurons in hippocampal and temporal and frontal regions of AD brains.

Alzheimer's disease is associated with disordered localization of ganglioside GM1 molecular species in the human dentate gyrus.

Alzheimer's disease (AD) is a progressive dementia associated with loss of memory and cognitive dysfunction. In a previous study, we demonstrated a decrease in b-series gangliosides along with a change in ganglioside molecular species in the hippocampal grey matter of patients with AD. The present study demonstrates the use of imaging mass spectrometry for analyzing the spatial arrangement of ganglioside GM1 (GM1) molecular species in the hippocampus.

Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins.

Proteogenomics of the human hippocampus: The road ahead.

The hippocampus is one of the most essential components of the human brain and plays an important role in learning and memory. The hippocampus has drawn great attention from scientists and clinicians due to its clinical importance in diseases such as Alzheimer's disease (AD), non-AD dementia, and epilepsy. Understanding the function of the hippocampus and related disease mechanisms requires comprehensive knowledge of the orchestration of the genome, epigenome, transcriptome, proteome, and post-translational modifications (PTMs) of proteins.

Large-scale analysis of posttranslational modifications in the hippocampus of patients with Alzheimer's disease using pI shift and label-free quantification without enrichment.

Posttranslational modifications modulate protein function in cells. Global analysis of multiple posttranslational modifications can provide insight into physiology and disease, but presents formidable challenges. In the present study, we used a technique that does not require target enrichment to analyze alterations in the phosphorylation and ubiquitination of proteins from patients with Alzheimer's disease (AD).

The uniqueness of biobanks for neurological and psychiatric diseases: potentials and pitfalls.

Objectives: Central nervous system (CNS) biobanks are facing difficult and specific challenges due to the sensitive issue of collecting specimens of the CNS, and especially the brain. At present, there is no global network/central database to serve researchers, clinicians and pharma companies, or to supply the special specimens and the accompanying data in sufficient numbers and detail, respectively. The main challenge/objective is to standardize and harmonize all the facets involved in CNS biobanking in order to maximize efficient sample collection.

Chromosome 11-centric human proteome analysis of human brain hippocampus tissue.

Human chromosome 11 is the third gene-rich chromosome having 1304 protein-coding genes. According to the GeneCards, this chromosome contains 240 genes related to diseases, as it is well known as a disease-rich chromosome. Although there are many protein-coding genes, the proteomic identification ratio is rather low.

Pitfalls and practicalities in collecting and banking human brain tissues for research on psychiatric and neulogical disorders.

It is essential to examine brain materials for the understanding the cause and pathology of mental disorders. Recent methodological progress urges us to set up well qualified brain banks. Human tissue and Bio-banking is a complex field and the daily practice of brain banks needs to abide by several golden standards in order to avoid pitfalls in basic research: 1) A donor system in which informed consent is granted for the use of the samples for scientific research, including genetic analysis and access to medical records, 2) Rapid autopsy system, 3) Compatibility of protocols for procurement, management, handling and storage, 4) A generally accepted consensus on diagnostic criteria, 5) Quality control, 6) Abiding by local/international legal and ethical guidelines for work with human material, 7) Proper safety procedures.

α-Synuclein mRNA and soluble α-synuclein protein levels in post-mortem brain from patients with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease.

α-Synuclein is a neuronal protein implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Whilst increased α-synuclein expression due to gene duplication or triplication can cause familial PD, previous studies of α-synuclein levels in idiopathic disease have produced conflicting data. We quantified α-synuclein mRNA and soluble protein in five human post-mortem brain regions from four groups of individuals with PD, DLB, Alzheimer's disease (AD) and matched controls.

Zinc transporter mRNA levels in Alzheimer's disease postmortem brain.

Zinc (Zn2+) is concentrated into pre-synaptic vesicles and co-released with neurotransmitter at some synapses. Zn2+ can accelerate assembly of the amyloid-β peptides (Aβ) and tau protein central to the neuropathological changes found in Alzheimer's disease (AD). Altered protein levels of the membrane Zn2+ transporters ZnT1, ZnT4, and ZnT6 have been reported in AD postmortem brain tissue.

Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease.

Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field.

[Changes of nuclear factor and inflammatory chemotactic factors in brain of patients with Alzheimer's disease].

Objectives: To investigate the changes of nuclear factor (NF-)κBp65 and inflammatory chemotactic factors including monocyte chemoattractant protein 1 (MCP-1/CCL-2), macrophage inflammatory protein 1α (MIP-1α/CCL-3), glial fibrillary acidic protein (GFAP) in brains of the patients with Alzheimer's disease (AD) and reveal the correlation of these factors.

Methods: Ten patients with AD and 8 age-matched control subjects were selected in the study. Immunohistochemistry was performed to determine the protein expression of NF-κBp65, MCP-1, MIP-1α and GFAP.

The human face of biobank networks for translational research.

The biobanking literature frequently addresses donor and societal issues surrounding biobanking, but the biobanker's perspective is rarely highlighted. While not comprehensive, this article offers an overview of the human aspects of biobanking from the viewpoint of biobank personnel-from biobank formation, through the process, and in addressing post-biobanking issues. As every biobank and biobank network may differ, such factors may vary.

BACE1 mRNA expression in Alzheimer's disease postmortem brain tissue.

β-site AβPP cleaving enzyme 1 (BACE1) catalyses the rate-limiting step for production of amyloid-β (Aβ) peptides, involved in the pathological cascade underlying Alzheimer's disease (AD). Elevated BACE1 protein levels and activity have been reported in AD postmortem brains. Our study explored whether this was due to elevated BACE1 mRNA expression.

Changed clathrin regulatory proteins in the brains of Alzheimer's disease patients and animal models.

In the study, the expression of clathrin regulatory proteins dynamin I, AP180, and synaptic vesicle protein synaptophysin in multiple brain regions of the patients with Alzheimer's disease (AD), the transgenic mice carrying the Swedish mutation of amyloid-β protein precursor (AβPP) 670/671 (AβPPSWE), and the rats injected by bilateral hippocampus with amyloid-β peptide (Aβ)1-42 were examined by immunohistochemistry and Nissl staining, Western blotting, and Real-time PCR, respectively. Spatial learning and memory of the rats were evaluated by Morris Water Maze test, and the ability of endocytosis in the cultured rat hippocampal neurons was detected by FM1-43 fluorescence imaging. Significant decreases in protein levels of dynamin I, AP180, and synaptophysin were observed in both AD patients and mice with AβPPSWE as compared to controls.

A meta-analysis of two-dimensional electrophoresis pattern of the Parkinson's disease-related protein DJ-1.

Motivation: The two-dimensional electrophoresis (2-DE) pattern of proteins is thought to be specifically related to the physiological or pathological condition at the moment of sample preparation. On this ground, most proteomic studies move to identify specific hallmarks for a number of different conditions. However, the information arising from these investigations is often incomplete due to inherent limitations of the technique, to extensive protein post-translational modifications and sometimes to the paucity of available samples.

Whole genome association analysis shows that ACE is a risk factor for Alzheimer's disease and fails to replicate most candidates from Meta-analysis.

For late onset Alzheimer's disease (LOAD), the only confirmed, genetic association is with the apolipoprotein E (APOE) locus on chromosome 19. Meta-analysis is often employed to sort the true associations from the false positives. LOAD research has the advantage of a continuously updated meta-analysis of candidate gene association studies in the web-based AlzGene database.

ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain.

Background: ZnT3 is a membrane Zn(2+ )transporter that is responsible for concentrating Zn(2+ )into neuronal presynaptic vesicles. Zn(2+ )homeostasis in the brain is relevant to Alzheimer's disease (AD) because Zn(2+ )released during neurotransmission may bind to Abeta peptides, accelerating the assembly of Abeta into oligomers which have been shown to impair synaptic function.

Results: We quantified ZnT3 mRNA levels in Braak-staged human post mortem (pm) brain tissue from medial temporal gyrus, superior occipital gyrus, superior parietal gyrus, superior frontal gyrus and cerebellum from individuals with AD (n = 28), and matched controls (n = 5) using quantitative real-time PCR.

Comprehensive mRNA expression profiling distinguishes tauopathies and identifies shared molecular pathways.

Background: Understanding the aetiologies of neurodegenerative diseases such as Alzheimer's disease (AD), Pick's disease (PiD), Progressive Supranuclear Palsy (PSP) and Frontotemporal dementia (FTD) is often hampered by the considerable clinical and molecular overlap between these diseases and normal ageing. The development of high throughput genomic technologies such as microarrays provide a new molecular tool to gain insight in the complexity and relationships between diseases, as they provide data on the simultaneous activity of multiple genes, gene networks and cellular pathways.

Methodology/principal Findings: We have constructed genome wide expression profiles from snap frozen post-mortem tissue from the medial temporal lobe of patients with four neurodegenerative disorders (5 AD, 5 PSP, 5 PiD and 5 FTD patients) and 5 control subjects.

Biobanks for biomarkers in neurological disorders: the Da Vinci bridge for optimal clinico-pathological connection.

The diagnosis of dementing disorders is severely hampered by the absence of reliable biomarkers that can be measured in body fluids such as blood, urine and cerebro-spinal fluid (CSF). Searching for biomarkers is hampered by the huge variability between individuals; the use of autopsy specimens induces significant data fluctuation due to rapid post-mortem changes in the specimens. The search for biomarkers obtained from living donors has contributed already a vast amount of data.

Evidence for an association between KIBRA and late-onset Alzheimer's disease.

We recently reported evidence for an association between the individual variation in normal human episodic memory and a common variant of the KIBRA gene, KIBRA rs17070145 (T-allele). Since memory impairment is a cardinal clinical feature of Alzheimer's disease (AD), we investigated the possibility of an association between the KIBRA gene and AD using data from neuronal gene expression, brain imaging studies, and genetic association tests. KIBRA was significantly over-expressed and three of its four known binding partners under-expressed in AD-affected hippocampal, posterior cingulate and temporal cortex regions (P<0.

Standard Operating Procedures, ethical and legal regulations in BTB (Brain/Tissue/Bio) banking: what is still missing?

The use of human biological specimens in scientific research is the focus of current international public and professional concern and a major issue in bioethics in general. Brain/Tissue/Bio banks (BTB-banks) are a rapid developing sector; each of these banks acts locally as a steering unit for the establishment of the local Standard Operating Procedures (SOPs) and the legal regulations and ethical guidelines to be followed in the procurement and dissemination of research specimens. An appropriat Code of Conduct is crucial to a successful operation of the banks and the research application they handle.