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Article
Open AccessGenetic drivers of heterogeneity in type 2 diabetes pathophysiology
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic c...
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Article
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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Article
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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Article
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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Article
Open AccessGenetic insights into resting heart rate and its role in cardiovascular disease
Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associate...
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Article
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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Article
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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Article
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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Article
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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Open AccessAuthor Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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Article
Open AccessGenome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers
Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer’s disease (AD) more directly than clinical diagnosis. Initiated b...
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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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Article
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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Article
Open AccessMutation analysis of disease causing genes in patients with early onset or familial forms of Alzheimer’s disease and frontotemporal dementia
Most dementia disorders have a clear genetic background and a number of disease genes have been identified. Mutations in the tau gene (MAPT) lead to frontotemporal dementia (FTD), whereas mutations in the genes f...
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Article
Open AccessAstroglial tracer BU99008 detects multiple binding sites in Alzheimer’s disease brain
With reactive astrogliosis being established as one of the hallmarks of Alzheimer’s disease (AD), there is high interest in develo** novel positron emission tomography (PET) tracers to detect early astrocyte...
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Article
Open AccessAmyloid, tau, and astrocyte pathology in autosomal-dominant Alzheimer’s disease variants: AβPParc and PSEN1DE9
Autosomal-dominant Alzheimer’s disease (ADAD) may be associated with atypical amyloid beta deposits in the brain. In vivo amyloid imaging using 11C-Pittsburgh compound B (PiB) tracer has shown differences in bind...
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Article
Open AccessLeukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99
Mosaic loss of chromosome Y (LOY) in immune cells is a male-specific mutation associated with increased risk for morbidity and mortality. The CD99 gene, positioned in the pseudoautosomal regions of chromosomes X ...
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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, ...
