Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis.

Mass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches.

Distinctive alteration of presynaptic proteins in the outer molecular layer of the dentate gyrus in Alzheimer's disease.

Synaptic degeneration has been reported as one of the best pathological correlates of cognitive deficits in Alzheimer's disease. However, the location of these synaptic alterations within hippocampal sub-regions, the vulnerability of the presynaptic versus postsynaptic compartments, and the biological mechanisms for these impairments remain unknown. Here, we performed immunofluorescence labelling of different synaptic proteins in fixed and paraffin-embedded human hippocampal sections and report reduced levels of several presynaptic proteins of the neurotransmitter release machinery (complexin-1, syntaxin-1A, synaptotagmin-1 and synaptogyrin-1) in Alzheimer's disease cases.

Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE-ε4/TOMM40 long poly-T repeat allele variants.

Introduction: The role of 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).

Methods: We dissected genetic profiles within the region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls.

The Proteome of the Dentate Terminal Zone of the Perforant Path Indicates Presynaptic Impairment in Alzheimer Disease.

Synaptic dysfunction is an early pathogenic event in Alzheimer disease (AD) that contributes to network disturbances and cognitive decline. Some synapses are more vulnerable than others, including the synapses of the perforant path, which provides the main excitatory input to the hippocampus. To elucidate the molecular mechanisms underlying the dysfunction of these synapses, we performed an explorative proteomic study of the dentate terminal zone of the perforant path.

Non-specific Detection of a Major Western Blotting Band in Human Brain Homogenates by a Multitude of Amyloid Precursor Protein Antibodies.

The use of human post-mortem brain material is of great value when investigating which pathological mechanisms occur in human brain, and to avoid translational problems which have for example been evident when translating animal research into Alzheimer disease (AD) clinical trials. The amyloid β (Aβ)-peptide, its amyloid precursor protein (APP) and the intermediate APP-c-terminal fragments (APP-CTFs) are all important players in AD pathogenesis. In order to elucidate which APP CTF that are the most common in brain tissue of different species and developmental stages, and whether there are any differences in these fragments between AD and control brain, we investigated the occurrence of these fragments using different APP c-terminal antibodies.

DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study.

Background: Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13-30% in Ashkenazi Jewish populations, and 30-40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance.

Expression changes of genes associated with apoptosis and survival processes in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of the dopaminergic neurons in substantia nigra, presumably due to increased apoptosis and oxidative stress. To investigate whether PD-induced survival/apoptosis gene expression changes can serve as prognostic biomarkers of PD, we measured expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway factors and additional apoptotic and anti-apoptotic factors in peripheral blood mononuclear cells (PBMC) of PD patients (n=50) and healthy controls (n=50) by real time PCR. Expression levels of apoptotic factors phosphatase and tensin homolog (PTEN) and mitochondrial apoptosis-inducing factor 1 (AIFM1) were significantly decreased, anti-apoptotic factors DJ-1 and Akt-1 were significantly increased and anti-apoptotic Bcl-2 was significantly decreased in PD patients.

Evaluation of incidence and clinical features of antibody-associated autoimmune encephalitis mimicking dementia.

Background: Anti-neuronal autoimmunity may cause cognitive impairment that meets the criteria for dementia. Objective. Our aim was to detect the incidence and clinical features of autoimmune encephalitis imitating clinical findings of primary dementia disorders and to delineate the validity of anti-neuronal antibody screening in dementia patients.

Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease.

Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.

Identification of a novel BRCA2 and CHEK2 A-C-G-C haplotype in Turkish patients affected with breast cancer.

Background: Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk.

Methods: We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls.