Takashi Saito

Cryo-EM structure of pro-aggregant P301L/S320F double-mutant tau filaments formed in mouse brains following peripheral AAV delivery

The paper reports a cryo-EM structure of P301L/S320F double-mutant tau filaments induced in mice via peripheral AAV delivery, revealing a novel filament fold distinct from known tauopathies.

CXCL10 drives female-specific tau pathology progression and defines sex-dependent vulnerability in tauopathy model mice

This study identifies CXCL10 as a driver of female-specific tau pathology progression in tauopathy model mice, revealing a sex-dependent mechanism independent of T cell or glial activation.

Trem2 R47H mutation shows mild, but functionally divergent alterations in microglial phenotypes compared to Trem2 deficiency in aged AppNL-F knock-in mice

This study compares the effects of TREM2 R47H mutation and TREM2 deficiency in aged AppNL-F mice, finding that the mutation causes mild, functionally distinct microglial changes compared to a null effect.

Alzheimer disease beta-amyloid pathology accelerates age-related hearing loss: evidence from AppNL-F 'knock-in' mice

This study shows that Alzheimer's beta-amyloid pathology accelerates age-related hearing loss in a mouse model, with increased hearing thresholds, outer hair cell loss, and damage to the stria vascularis.

Involvement of orexin nerves in early stage of Alzheimer's disease model mice and preventive effect of orexin receptor antagonists

This study investigates the effect of orexin receptor antagonists on early-stage Alzheimer's disease in mice, finding they prevent cognitive impairment and amyloid-beta accumulation.

Humanized tau and amyloid-β deposition accelerate tau propagation, neuronal cell loss and neurophysiological dysfunction in novel mouse models of primary age-related tauopathy and Alzheimer's disease

This study shows that human tau and amyloid-β pathology alter tau propagation patterns and cause neurophysiological dysfunction in mouse models of tauopathy and Alzheimer's disease.

Fus depleted oligodendrocytes reduce neuronal damage and attenuate AD progression in the AppNL-G-F mouse

The paper shows that enhancing oligodendrocyte function in a mouse model of Alzheimer's Disease reduces neuronal damage and slows disease progression.

Divergent Effects of APOE3 and APOE4 Human Astrocytes on Key Alzheimer's Disease Hallmarks in Chimeric Mice

This study shows that APOE3 and APOE4 human astrocytes differentially affect Alzheimer's disease hallmarks in chimeric mice, with APOE3 reducing and APOE4 worsening pathology.

Age- and amyloid-β-dependent initiation of neurofibrillary tau tangles: NLFTaum/h, an improved mouse model of Alzheimer's disease without mutations in MAPT

This paper introduces a new mouse model, NLFTaum/h, that shows ageing and amyloid-β can initiate tau pathology without MAPT mutations, revealing interactions between age, Aβ, and human tau.

Metabolic resistance of Abeta3pE-42, epitope of the anti-Alzheimer therapeutic antibody, donanemab.

This paper investigates the metabolic stability and deposition of A{beta}3pE-42, a target of the Alzheimer's antibody donanemab, showing it is more stable than other A{beta}X-42 species and accumulates with age.

Oligodendrocytes and neurons contribute to amyloid-β deposition in Alzheimer's disease

The paper shows oligodendrocytes contribute to amyloid-β plaques in Alzheimer's disease, but neurons are required for plaque formation.

Divergent age-dependent conformational rearrangement within Aβ-amyloid deposits in APP23, APPPS1, and AppNL-F mice

This paper compares Aβ fibril structures in three mouse models of Alzheimer's disease, finding age-dependent differences in plaque morphology and polymorph maturation.

Cystatin F (Cst7) drives sex-dependent changes in microglia in an amyloid-driven model of Alzheimer's Disease

This study investigates the sex-specific role of Cst7 in microglia in an amyloid-driven Alzheimer's Disease model, finding sexually dimorphic effects on endolysosomal function and inflammation.

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

The paper shows TSPO expression increases in activated microglia in rodent models but not in human neurodegenerative diseases, indicating species-specific differences in TSPO function.

Ageing-associated myelin dysfunction drives amyloid deposition in mouse models of Alzheimer's disease

This study shows that ageing-related myelin dysfunction drives amyloid-beta deposition in Alzheimer's disease mouse models, suggesting myelin integrity as an upstream risk factor.

Alterations to parvalbumin-expressing interneuron function and associated network oscillations in the hippocampal - medial prefrontal cortex circuit during natural sleep in APPNL-G-F mice

This study examines network impairments in APPNL-G-F mice during sleep, finding NREM-specific changes in mPFC spindles and hippocampal SWRs linked to PV interneuron dysfunction.

Accumulation of m6A exhibits stronger correlation with MAPT than beta-amyloid pathology in an APP NL-G-F /MAPT P301S mouse model of Alzheimer's disease

This study shows that m6A accumulation correlates more strongly with MAPT pathology than beta-amyloid in an Alzheimer's mouse model.

Cryo-EM structures of amyloid-beta filaments with the Arctic mutation (E22G) from human and mouse brains

The paper reports cryo-EM structures of amyloid-beta filaments with the Arctic mutation from human and mouse brains, revealing structural differences and conformational changes.

Genetic mapping of APP and amyloid-β biology modulation by trisomy 21

This study identifies chromosome 21 genes other than APP that modulate amyloid-β accumulation in Down syndrome mouse models.

A novel fully-automated system for lifelong continuous phenotyping of mouse cognition and behaviour

This paper introduces an automated AI-driven system for continuous phenotyping of mouse cognition and behaviour, showing it can distinguish hippocampal and Alzheimer's models better than standard tests.

Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters

The paper identifies Sirt2-induced H4K16ac deacetylation of Fzd1 and Fzd7 promoters as a mechanism repressing Wnt signaling in Alzheimer's disease.

Early memory deficits and extensive brain network disorganization in the AppNL-F/MAPT double knock-in mouse model of familial Alzheimer's disease.

This study uses an AD mouse model to show early memory deficits and brain network disorganization linked to specific neuropathology.

Young APPKI NL-G-F/NL-G-F mice display high-fat diet-induced metabolic disturbances and specific disorders associated with brain energy homeostasis.

This study shows that high-fat diet in early life causes metabolic disturbances in young AD mouse models but not neurological disorders.

Identification and drug-induced reversion of molecular signatures of Alzheimers disease onset and progression in AppNL-G-F, AppNL-F and 3xTg-AD mouse models

The paper identifies molecular signatures of Alzheimer's disease in AD mouse models and finds drugs that reverse these signatures and cognitive impairment.

Neprilysin-sensitive amyloidogenic Aβ versus IDE-sensitive soluble Aβ: a probable mechanistic cause for sporadic Alzheimer's disease

This study compares the roles of NEP and IDE in Aβ metabolism using double knockout mice, finding NEP primarily degrades insoluble Aβ and its deficiency contributes to AD pathology.

An isogenic panel of single App knock-in mouse models of Alzheimer's disease confers differential profiles of β-secretase inhibition and endosomal abnormalities

This study develops App knock-in mice without Swedish mutations to investigate β-secretase inhibition and endosomal abnormalities in Alzheimer's disease.

New App knock-in mice that accumulate wild-type human Aβ as rapidly as AppNL-G-F mice exhibit intensive cored plaque pathology and neuroinflammation.

This paper introduces a new mouse model that accumulates wild-type human Aβ rapidly, showing more severe cored plaque pathology and neuroinflammation than existing models.

Amyloid plaque deposition accelerates tau propagation via activation of microglia in a humanized APP mouse model

The paper shows that amyloid plaques accelerate tau propagation in mice by activating microglia, which secrete more extracellular vesicles.

The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research

This study shows that the AppNL-G-F mouse retina accumulates Aβ early and exhibits AD-like features, suggesting it as a model for preclinical AD research and diagnosis.

α-Endosulfine regulates amyloid β42 via the modulation of neprilysin activity

This study identifies α-endosulfine as a negative regulator of neprilysin activity, showing that its deficiency reduces amyloid β42 deposition in Alzheimer's disease models.