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Article
Open AccessPlasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS
Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) ...
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Article
Open AccessDifferent inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition
Neuroinflammation is a hallmark of Alzheimer’s disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been describe...
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Article
Open AccessExploring the ATN classification system using brain morphology
The NIA-AA proposed amyloid-tau-neurodegeneration (ATN) as a classification system for AD biomarkers. The amyloid cascade hypothesis (ACH) implies a sequence across ATN groups that patients might undergo durin...
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Article
Open AccessBrain reserve contributes to distinguishing preclinical Alzheimer’s stages 1 and 2
In preclinical Alzheimer’s disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we...
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Article
Open AccessSerum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer’s disease: results from the DELCODE study
Neuroinflammation constitutes a pathological hallmark of Alzheimer’s disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based b...
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Article
Open AccessImproving 3D convolutional neural network comprehensibility via interactive visualization of relevance maps: evaluation in Alzheimer’s disease
Although convolutional neural networks (CNNs) achieve high diagnostic accuracy for detecting Alzheimer’s disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clini...
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Article
Open AccessThe BDNFVal66Met SNP modulates the association between beta-amyloid and hippocampal disconnection in Alzheimer’s disease
In Alzheimer’s disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNFVal66Met) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on ne...
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Protocol
Proteome Analysis with Classical 2D-PAGE
Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) is based on the combination of two orthogonal separation techniques. In the first dimension, proteins are separated by their isoelectric point, a te...
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Protocol
Differential Proteome Analysis Using 2D-DIGE
Classical 2D-PAGE allows comparison and quantitation of proteomes by visualization of protein patterns using gel stains and comparative image analysis. The introduction of fluorescent reagents for protein labe...
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Article
Open AccessNeuropsychiatric symptoms in at-risk groups for AD dementia and their association with worry and AD biomarkers—results from the DELCODE study
Early identification of individuals at risk of dementia is mandatory to implement prevention strategies and design clinical trials that target early disease stages. Subjective cognitive decline (SCD) and neuro...
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Article
Open AccessPLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment
A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer’s disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. ...
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Article
NLRP3 inflammasome activation drives tau pathology
Alzheimer’s disease is characterized by the accumulation of amyloid-beta in plaques, aggregation of hyperphosphorylated tau in neurofibrillary tangles and neuroinflammation, together resulting in neurodegenera...
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Article
Dysregulation of TLR5 and TAM Ligands in the Alzheimer’s Brain as Contributors to Disease Progression
The hypothesis that accumulation of beta-amyloid (Aβ) species in the brain represents a major event in Alzheimer’s disease (AD) pathogenesis still prevails; nevertheless, an array of additional pathological pr...
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Article
Open AccessWhich features of subjective cognitive decline are related to amyloid pathology? Findings from the DELCODE study
Subjective cognitive decline (SCD) has been proposed as a pre-MCI at-risk condition of Alzheimer’s disease (AD). Current research is focusing on a refined assessment of specific SCD features associated with in...
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Article
Open AccessCharacterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer’s disease
Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer’s disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during th...
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Article
Open AccessDesign and first baseline data of the DZNE multicenter observational study on predementia Alzheimer’s disease (DELCODE)
Deep phenoty** and longitudinal assessment of predementia at-risk states of Alzheimer’s disease (AD) are required to define populations and outcomes for dementia prevention trials. Subjective cognitive decli...
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Article
Open AccessTau plasma levels in subjective cognitive decline: Results from the DELCODE study
Previous studies have demonstrated increased tau plasma levels in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) due to AD. Much less is known whether increased tau plasma levels ca...
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Protocol
Isolating Peripheral Lymphocytes by Density Gradient Centrifugation and Magnetic Cell Sorting
Combining density gradient centrifugation with magnetic cell sorting provides a powerful tool to isolate blood cells with high reproducibility, yield, and purity. It also allows for subsequent separation of mu...
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Article
Open AccessBody Fluid Cytokine Levels in Mild Cognitive Impairment and Alzheimer’s Disease: a Comparative Overview
This article gives a comprehensive overview of cytokine and other inflammation associated protein levels in plasma, serum and cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD) and mild cognit...
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Protocol
Differential Proteome Analysis Using 2D-DIGE
Classical two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) allows comparison and quantitation of proteomes by visualization of protein patterns using gel stains and comparative image analysis. The...