Improving vulnerable Calbindin1− neurons in the ventral hippocampus rescues tau-induced impairment of episodic memory DOI Creative Commons
Huiyang Lei,

Jingru Lv,

Fuqiang Zhang

и другие.

Translational Neurodegeneration, Год журнала: 2025, Номер 14(1)

Опубликована: Март 4, 2025

Intraneuronal accumulation of hyperphosphorylated tau is a hallmark Alzheimer's disease (AD). Given the significant correlation between pathology and memory loss in AD patients, identifying vulnerable brain regions, particularly susceptible neuron types these will advance our understanding onset shed light on therapeutic strategies to manage its progression. Immunofluorescent staining was employed identify regions AD. A combination chemogenetics, electrophysiological recording, vivo Ca2+ modified temporal-order discrimination behavior test utilized investigate toxicity neurons dorsal part ventral hippocampus. Proteomics, phosphoproteomics, molecular targeting were used explore underlying mechanisms susceptibility The beneficial effects microtubule affinity regulating kinase 4 (MARK4) knockdown administration DEPhosphorylation TArgeting Chimera (DEPTAC) evaluated mice with pathology. In postmortem brains we observed robust anterior hippocampal CA1 region, Calbindin1- (Calb1-) neurons, as opposed posterior region Calb1+ neurons. Calb1- phospho-tau also P301L mice, especially (anterior human) (dvCA1). dvCA1 displayed distinct protein phosphorylated networks compared CA1, accompanied by overactivation MARK4. Overexpressing human (dvCA1Calb1- neurons) specifically impairs objects. Meanwhile, significantly inhibited excitability firing patterns dvCA1Calb1- associated discrimination. Knocking down MARK4 or reducing hyperphosporylated via DEPTAC ameliorated AD-like improved These findings highlight crucial role early stage demonstrate potential through counter vulnerability and, consequently, ameliorate episodic deficits

Язык: Английский

Complement-mediated synapse loss in Alzheimer’s disease: mechanisms and involvement of risk factors DOI

Lang Wen,

Danlei Bi,

Yong Shen

и другие.

Trends in Neurosciences, Год журнала: 2023, Номер 47(2), С. 135 - 149

Опубликована: Дек. 20, 2023

Язык: Английский

Процитировано

10
Tau seeds from Alzheimer's disease brains trigger tau spread in macaques while oligomeric‐Aβ mediates pathology maturation DOI Creative Commons
Morgane Darricau, Changsong Dou, Rémi Kinet

и другие.

Alzheimer s & Dementia, Год журнала: 2023, Номер 20(3), С. 1894 - 1912

Опубликована: Дек. 26, 2023

The "prion-like" features of Alzheimer's disease (AD) tauopathy and its relationship with amyloid-β (Aβ) have never been experimentally studied in primates phylogenetically close to humans.

Язык: Английский

Процитировано

10
PM2.5 triggers tau aggregation in a mouse model of tauopathy DOI Creative Commons
Congcong Liu, Lanxia Meng,

Yan Gao

и другие.

JCI Insight, Год журнала: 2024, Номер 9(14)

Опубликована: Июль 21, 2024

The aggregation and prion-like propagation of tau are the hallmarks Alzheimer's disease (AD) other tauopathies. However, molecular mechanisms underlying assembly spread pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk AD. unknown. Here, we showed PM2.5 triggered promoted formation fibrils. Injection PM2.5-induced preformed fibrils (PFFs) into hippocampus P301S transgenic mice induced cognitive deficits synaptic dysfunction. Furthermore, intranasal administration exacerbated impairment in mice. In conclusion, our results indicated impairments. These provide mechanistic insight how increases

Язык: Английский

Процитировано

4
Astrocyte–Neuron Interactions in Alzheimer’s Disease DOI
Clara Muñoz‐Castro, Alberto Serrano‐Pozo

Advances in neurobiology, Год журнала: 2024, Номер unknown, С. 345 - 382

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

3
Compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one downregulation of Galectin-3 ameliorates Aβ pathogenesis-induced neuroinflammation in 5 × FAD mice DOI
Xueyan Liu,

Ping Chen,

Wei Wu

и другие.

Life Sciences, Год журнала: 2024, Номер 357, С. 123085 - 123085

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

3
CSF complement proteins are elevated in prodromal to moderate Alzheimer's disease patients and are not altered by the anti‐tau antibody semorinemab DOI Creative Commons

Cosme Sandoval,

Julie Lee, Balázs István Tóth

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(11), С. 7940 - 7953

Опубликована: Окт. 6, 2024

Abstract INTRODUCTION Growing evidence suggests a role for neuroinflammation in Alzheimer's disease (AD). We investigated complement pathway activity AD patient cerebrospinal fluid (CSF) and evaluated its modulation by the anti‐tau antibody semorinemab. METHODS Immunoassays were applied to measure CSF proteins C4, factor B (FB), C3 their cleavage fragments C4a, C3a, Bb (Bb) patients separate cognitively unimpaired (CU) cohort. RESULTS All measured increased versus CU subjects, with C4a displaying most robust increase. Finally, semorinemab did not have significant pharmacodynamic effect on proteins. DISCUSSION Elevated levels of C3, Bb, FB are consistent activation brains. Despite showing reduction soluble tau species, impact protein or activity. Further studies needed determine value as biomarkers AD. Highlights Cerebrospinal (AD) compared Baseline correlated neuro‐axonal degeneration glial patients. The investigational relative placebo arm.

Язык: Английский

Процитировано

3
Longitudinal synaptic loss versus tau Braak staging in amnestic mild cognitive impairment DOI Creative Commons
Greet Vanderlinden, Michel Koole, Laura Michiels

и другие.

Alzheimer s & Dementia, Год журнала: 2024, Номер unknown

Опубликована: Дек. 28, 2024

Abstract INTRODUCTION The longitudinal progression of synaptic loss in Alzheimer's disease (AD) and how it is affected by tau pathology remains poorly understood. METHODS Thirty patients with amnestic mild cognitive impairment (aMCI) 26 healthy controls underwent evaluations tau, vesicle protein 2A (SV2A), amyloid positron emission tomography. Twenty‐one aMCI 2‐year follow‐up (FU) investigations. RESULTS Tau levels increased longitudinally Braak regions III through VI but not I II. SV2A decreased all aMCI. Baseline was negatively associated early at FU across regions. change were decline. DISCUSSION accumulation reaches a plateau already the stage AD. In regions, association between baseline might reflect dysfunction caused pathology. Highlights reached patients. show widespread decrease (SV2A) over 2 years. predictive for loss. tau–SV2A relation showed individual variability negative cognition.

Язык: Английский

Процитировано

3
Higher plasma total tau concentrations among patients reporting CNS-related side effects from antiseizure medication DOI Creative Commons
Klara Andersson, Sarah Akel, Fredrik Asztély

и другие.

Seizure, Год журнала: 2025, Номер 125, С. 99 - 105

Опубликована: Янв. 13, 2025

Side effects from antiseizure medication (ASM) are common in epilepsy but biomarkers for detection and monitoring missing. This study investigated associations between CNS-related side ASM blood concentrations of the brain injury markers neurofilament-light (NFL), total tau, glial acidic fibrillary protein (GFAP), S100 calcium-binding B (S100B) neuron-specific enolase (NSE). is a population-based cohort adults with recruited five Swedish outpatient neurology clinics December 2020 to April 2023. classified as CNS-related: tiredness, dizziness, headache, concentration, memory, mood, motor/tremor, or sleep. Marker groups CNS effects/no were analyzed Mann-Whitney U-test significant differences included multivariable logistic regression models adjusting age, duration, seizure status, acquired structural lesion, mono-/polytherapy. The consisted 367 patients, 187 (51 %) females, median age was 43 years (IQR 30-61), 123 (34 reported effects. Total tau higher among participants reporting (median 4.44 (95 %CI 4.12-4.88) pg/ml) compared without (3.84 3.52-4.07) pg/ml, p < 0.01). difference remained models. NSE did not remain model. No observed NFL, GFAP S100B. Higher plasma concentration could be associated increased risk ASM. Longitudinal studies determine if this reflects vulnerability detrimental PREDICT, clinicaltrials.gov identifier NCT04559919.

Язык: Английский

Процитировано

0
Novel synaptic markers predict early tau pathology and cognitive deficit in an asymptomatic population at risk of Alzheimer’s disease DOI

Jiarui Ao,

Cynthia Picard, Daniel Auld

и другие.

Molecular Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 18, 2025

Язык: Английский

Процитировано

0
Tau oligomers impair memory and synaptic plasticity through the cellular prion protein DOI Creative Commons
Claudia Balducci, Franca Orsini, Milica Cerovic

и другие.

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 27, 2025

Deposition of abnormally phosphorylated tau aggregates is a central event leading to neuronal dysfunction and death in Alzheimer's disease (AD) other tauopathies. Among aggregates, oligomers (TauOs) are considered the most toxic. AD brains show significant increase TauOs compared healthy controls, their concentration correlating with severity cognitive deficits progression. In vitro vivo TauO exposure leads synaptic dysfunction, but mechanisms action unclear. Evidence suggests that cellular prion protein (PrPC) may act as mediator neurotoxicity, previously proposed for β-amyloid α-synuclein oligomers. To investigate whether PrPC mediates detrimental activities, we effects on memory plasticity wild type (WT) knockout (Prnp0/0) mice. Intracerebroventricular injection significantly impaired recognition WT not Prnp0/0 Similarly, inhibited long-term potentiation acute hippocampal slices from Surface plasmon resonance indicated high-affinity binding between KD 20–50 nM. Immunofluorescence analysis naïve PrPC-overexpressing HEK293 cells exposed showed dose-dependent association over time, co-localization plasma membrane intracellular compartments, suggesting PrPC-may play role internalization. These findings support concept activities through direct interaction, targeting this interaction might be promising therapeutic strategy

Язык: Английский

Процитировано

0