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The existence of Aβ strains and their potential for driving phenotypic heterogeneity in Alzheimer’s disease
Reminiscent of the human prion diseases, there is considerable clinical and pathological variability in Alzheimer’s disease, the most common human neurodegenerative condition. As in prion disorders, protein mi...
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Article
Open AccessCommon variants in Alzheimer’s disease and risk stratification by polygenic risk scores
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curat...
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Article
Open AccessCrosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by brain accumulation of aggregated amyloid-beta (Aβ) and alpha-synuclein (αSYN), respectively. In order to develop effective therapies, ...
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Open AccessImmune cells lacking Y chromosome show dysregulation of autosomal gene expression
Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation a...
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Open AccessAccumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinson’s disease
Alpha-synuclein (α-syn) aggregation is the hallmark pathological lesion in brains of patients with Parkinson’s disease (PD) and related neurological disorders characterized as synucleinopathies. Accumulating e...
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Open AccessExtracellular vesicles from amyloid-β exposed cell cultures induce severe dysfunction in cortical neurons
Alzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that sp...
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Article
Open AccessSelf-reported difficulty initiating sleep and early morning awakenings are associated with nocturnal diastolic non-dip** in older white Swedish men
Chronically blunted nocturnal blood pressure (BP) dip** has been shown to increase the future risk of cardiovascular diseases. In the present cross-sectional study, we investigated whether self-reported inso...
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Article
Open AccessDual-task tests discriminate between dementia, mild cognitive impairment, subjective cognitive impairment, and healthy controls – a cross-sectional cohort study
Discrimination between early-stage dementia and other cognitive impairment diagnoses is central to enable appropriate interventions. Previous studies indicate that dual-task testing may be useful in such diffe...
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Open AccessAltered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers
The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. H...
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Article
α-Synuclein strains target distinct brain regions and cell types
The clinical and pathological differences between synucleinopathies such as Parkinson’s disease and multiple system atrophy have been postulated to stem from unique strains of α-synuclein aggregates, akin to w...
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Article
Genetic predisposition to mosaic Y chromosome loss in blood
Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1–5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational ...
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Article
Open AccessHigh levels of AAV vector integration into CRISPR-induced DNA breaks
Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In ...
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Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Open AccessBinding of α-synuclein oligomers to Cx32 facilitates protein uptake and transfer in neurons and oligodendrocytes
The intercellular transfer of alpha-synuclein (α-syn) has been implicated in the progression of Parkinson’s disease (PD) and multiple system atrophy (MSA). The cellular mechanisms underlying this process are n...
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Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Risk for late-onset Alzheimer’s disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinicall...
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Open AccessTransethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer’s disease
Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethniciti...
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Mosaic loss of chromosome Y in leukocytes matters
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Article
Fine-map** type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend th...
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Open AccessSecretion and Uptake of α-Synuclein Via Extracellular Vesicles in Cultured Cells
In Parkinson’s disease and other Lewy body disorders, the propagation of pathology has been accredited to the spreading of extracellular α-synuclein (α-syn). Although the pathogenic mechanisms are not fully un...
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Open AccessAlzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers
The gradual deterioration of cognitive functions in Alzheimer’s disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligomers of amy...