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View article: Phosphorylation at serine 214 correlates with tau seeding activity in an age-dependent manner in two mouse models for tauopathies and is required for tau transsynaptic propagation
Phosphorylation at serine 214 correlates with tau seeding activity in an age-dependent manner in two mouse models for tauopathies and is required for tau transsynaptic propagation Open
Background Tau aggregation and propagation are hallmark features of Alzheimer's disease and related tauopathies. The molecular identity and post-translational modifications that contribute to tau seeding activity remain incompletely unders…
View article: Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer’s disease across model systems
Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer’s disease across model systems Open
SUMMARY Tau aggregates propagate through the brain in a prion-like manner in Alzheimer’s disease (AD) and other tauopathies, but the molecular identity and functional partners of the seeding-competent Tau species remain poorly defined. Her…
View article: Tau depletion diminishes vascular amyloid‐related deficits in a mouse model of cerebral amyloid angiopathy
Tau depletion diminishes vascular amyloid‐related deficits in a mouse model of cerebral amyloid angiopathy Open
INTRODUCTION Tau is essential for amyloid beta (Aβ)–induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. Cerebral amyloid angiopathy (CAA), a major vascular contributor to cog…
View article: Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling
Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling Open
INTRODUCTION Deciphering the diverse molecular mechanisms in living Alzheimer's disease (AD) patients is a big challenge but is pivotal for disease prognosis and precision medicine development. METHODS Utilizing an optimal transport approa…
View article: Tau ablation rescues vascular amyloid‐related deficits in a cerebral amyloid angiopathy model
Tau ablation rescues vascular amyloid‐related deficits in a cerebral amyloid angiopathy model Open
Background Close to 80 to 90% of subjects with AD also present cerebral amyloid angiopathy (CAA) a disease in which amyloid accumulation damages the vasculature an impairs blood flow. Since current AD therapies are targeting the disease fo…
View article: Protein degradation impairment and synapse elimination by microglia in BSN P3866A knock‐in mouse model of tauopathy
Protein degradation impairment and synapse elimination by microglia in BSN P3866A knock‐in mouse model of tauopathy Open
Background Tau aggregation is the major cause of several neurodegenerative tauopathies. Tau interaction with other proteins affects the formation of tau aggregates with seeding activity but less is known about its effects on tau‐seed prope…
View article: Enhanced microglial dynamics in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer’s disease
Enhanced microglial dynamics in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer’s disease Open
Background Asymptomatic Alzheimer’s disease (AsymAD) refers to individuals with preserved cognition but identifiable Alzheimer’s disease (AD) brain pathology, including beta‐amyloid (Aβ) deposits, neuritic plaques and neurofibrillary tangl…
View article: Interactome Analysis of Tau‐seed Isolated from AD Brains Suggests New Mechanism for Tau Aggregation and Spreading
Interactome Analysis of Tau‐seed Isolated from AD Brains Suggests New Mechanism for Tau Aggregation and Spreading Open
Background Tau aggregates, a hallmark of Alzheimer’s disease (AD) and other tauopathies, spread throughout the brain, contributing to neurodegeneration. How this propagation occurs remains elusive. Previous research suggests that tau‐seed …
View article: Optimal Transport‐Based Transcriptomic Mapping Revealed Atypical Disease Progression Subtypes in Living Alzheimer’s Disease Patients
Optimal Transport‐Based Transcriptomic Mapping Revealed Atypical Disease Progression Subtypes in Living Alzheimer’s Disease Patients Open
Background Alzheimer’s disease (AD) exhibits substantial heterogeneity in its disease trajectory. A subset of AD patients with unmatched cognitive decline/tauopathy severity has not been well studied. We identified such atypical subgroups …
View article: Optimal Transport‐Based Transcriptomic Mapping Revealed Atypical Disease Progression Subtypes in Living Alzheimer’s Disease Patients
Optimal Transport‐Based Transcriptomic Mapping Revealed Atypical Disease Progression Subtypes in Living Alzheimer’s Disease Patients Open
Background Alzheimer’s disease (AD) exhibits substantial heterogeneity in its disease trajectory. A subset of AD patients with unmatched cognitive decline/tauopathy severity has not been well studied. We identified such atypical subgroups …
View article: Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease
Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease Open
Asymptomatic Alzheimer’s disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer’s disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangl…
View article: Phosphorylation at serine 214 correlates with tau seeding activity in an age-dependent manner in two mouse models for tauopathies and is required for tau transsynaptic propagation
Phosphorylation at serine 214 correlates with tau seeding activity in an age-dependent manner in two mouse models for tauopathies and is required for tau transsynaptic propagation Open
Pathological aggregation and propagation of hyperphosphorylated and aberrant forms of tau are critical features of the clinical progression of Alzheimer’s disease and other tauopathies. To better understand the correlation between these pa…
View article: Therapeutic targeting of immunometabolism in Alzheimer’s disease reveals a critical reliance on Hexokinase 2 dosage on microglial activation and disease progression
Therapeutic targeting of immunometabolism in Alzheimer’s disease reveals a critical reliance on Hexokinase 2 dosage on microglial activation and disease progression Open
Summary Microgliosis and neuroinflammation are prominent features of Alzheimer’s disease (AD). Disease-responsive microglia meet their increased energy demand by reprogramming metabolism, specifically, switching to favor glycolysis over ox…
View article: Enhanced microglial dynamics and paucity of tau seeding in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer’s disease
Enhanced microglial dynamics and paucity of tau seeding in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer’s disease Open
Asymptomatic Alzheimer’s disease (AsymAD) describes the status of subjects with preserved cognition but with identifiable Alzheimer’s disease (AD) brain pathology (i.e. Aβ-amyloid deposits, neuritic plaques, and neurofibrillary tangles) at…
View article: TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo
TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo Open
The role of TREM2 in Alzheimer’s disease (AD) is not fully understood. Previous studies investigating the effect of TREM2 deletion on tauopathy mouse models without the contribution of b-amyloid have focused only on tau overexpression mode…
View article: The reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicity
The reduction of astrocytic tau prevents amyloid-β-induced synaptotoxicity Open
Alzheimer’s disease is a neurological disorder characterized by the overproduction and aggregation of amyloid-beta and the phosphorylation and intraneuronal accumulation of tau. These events promote synaptic dysfunction and loss, leading t…
View article: Activated endothelial cells induce a distinct type of astrocytic reactivity
Activated endothelial cells induce a distinct type of astrocytic reactivity Open
Reactive astrogliosis is a universal response of astrocytes to abnormal events and injuries. Studies have shown that proinflammatory microglia can polarize astrocytes (designated A1 astrocytes) toward a neurotoxic phenotype characterized b…
View article: BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model
BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model Open
Background An intronic GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in the C9ORF72 gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), referred to as C9ALS/FTD. No cure or effectiv…
View article: Widespread loss of the silencing epigenetic mark H3K9me3 in astrocytes and neurons along with hippocampal-dependent cognitive impairment in C9orf72 BAC transgenic mice
Widespread loss of the silencing epigenetic mark H3K9me3 in astrocytes and neurons along with hippocampal-dependent cognitive impairment in C9orf72 BAC transgenic mice Open
Background Hexanucleotide repeat expansions of the G 4 C 2 motif in a non-coding region of the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Tissues from C9ALS/FTD …
View article: Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice
Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice Open
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including…
View article: NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB‐P, and H3K27ac
NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB‐P, and H3K27ac Open
Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticit…
View article: Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons
Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons Open
Reelin, an extracellular glycoprotein secreted in embryonic and adult brain, participates in neuronal migration and neuronal plasticity. Extensive evidence shows that reelin via activation of the ApoER2 and VLDLR receptors promotes dendrit…