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Open AccessAstrocytic accumulation of tau fibrils isolated from Alzheimer’s disease brains induces inflammation, cell-to-cell propagation and neuronal impairment
Accumulating evidence highlights the involvement of astrocytes in Alzheimer’s disease (AD) progression. We have previously demonstrated that human iPSC-derived astrocytes ingest and modify synthetic tau fibril...
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Article
Open AccessAltered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion
Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer’s disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation pro...
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Open AccessCryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer’s disease
The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer’s disease. However, the properties of Aβ in such...
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Open AccessLevels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopa...
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Open AccessAltered Distribution of SNARE Proteins in Primary Neurons Exposed to Different Alpha-Synuclein Proteoforms
Growing evidence indicates that the pathological alpha-synuclein (α-syn) aggregation in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) starts at the synapses. Physiologic α-syn is involved in reg...
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Open AccessAstrocytic uptake of neuronal corpses promotes cell-to-cell spreading of tau pathology
Tau deposits in astrocytes are frequently found in Alzheimer’s disease (AD) and other tauopathies. Since astrocytes do not express tau, the inclusions have been suggested to be of neuronal origin. However, the...
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Open AccessThe G51D SNCA mutation generates a slowly progressive α-synuclein strain in early-onset Parkinson’s disease
Unique strains of α-synuclein aggregates have been postulated to underlie the spectrum of clinical and pathological presentations seen across the synucleinopathies. Whereas multiple system atrophy (MSA) is ass...
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Open AccessSize matters: the impact of nucleus size on results from spatial transcriptomics
Visium Spatial Gene Expression (ST) is a method combining histological spatial information with transcriptomics profiles directly from tissue sections. The use of spatial information has made it possible to di...
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the...
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Article
Open AccessNew insights into the genetic etiology of Alzheimer’s disease and related dementias
Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We per...
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Open AccessChallenges at the APOE locus: a robust quality control approach for accurate APOE genoty**
Genetic variants within the APOE locus may modulate Alzheimer’s disease (AD) risk independently or in conjunction with APOE*2/3/4 genotypes. Identifying such variants and mechanisms would importantly advance our ...
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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 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 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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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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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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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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Mosaic loss of chromosome Y in leukocytes matters
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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...