Post mortem validation and mechanistic study of UCB‐J in progressive supranuclear palsy patients’ brains DOI Creative Commons
Miriam Scarpa,

Elisavet Vallera,

Sira Ausellé‐Bosch

и другие.

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

Опубликована: Дек. 13, 2024

Abstract INTRODUCTION Progressive supranuclear palsy (PSP) is a devastating 4R tauopathy affecting motor functions and often misdiagnosed/underdiagnosed due to lack of specific biomarkers. Synaptic loss an eminent feature tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB‐J holds great potential for early diagnosis; however, there substantial knowledge gap in terms the mechanism extent nature METHODS Here, we report in‐depth post mortem validation mechanistic study PSP control brains using radioligand/autoradiography binding studies, alongside biochemical correlation analyses markers. RESULTS AND DISCUSSION 3 H‐UCB‐J targeted vesicle protein 2A with high specificity demonstrated distinct interrelation markers patients’ brain regions. The severely affected globus pallidus revealed deficits glutamate/GABAergic terminals. Cortical subcortical tau load differentially impacted marker profiles across patients, warranting further investigation. Highlights progressive conserved single nM site different depicted prominent at synaptosome levels terminals as compared control. distinctly influenced profile patients highlighted that presynaptic “ubiquitous” individually might not be able represent complete state deficits/loss brains.

Язык: Английский

The dual role of microglia in Alzheimer’s disease: from immune regulation to pathological progression DOI Creative Commons
Cong He, Baojiang Chen,

Hecai Yang

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Март 27, 2025

Alzheimer’s disease (AD) is a widespread neurodegenerative disorder and one of the major challenges for public health. Despite extensive research, role microglia in AD remains complex dual. The aim this review to summarize most recent advances research regarding dual concerning both immunomodulation pathological progression by considering mechanisms activation microglia, effects on Aβ clearance, tau pathology, impacts due genetic variations microglial functions. Among these findings are status M1 M2 phenotypes, crucial that variants like TREM2 have modulating response microglia. This describes how modulation signaling pathway might be exploited therapeutically treatment underlines relevance personalized medicine approach.

Язык: Английский

Процитировано

0
Post mortem validation and mechanistic study of UCB‐J in progressive supranuclear palsy patients’ brains DOI Creative Commons
Miriam Scarpa,

Elisavet Vallera,

Sira Ausellé‐Bosch

и другие.

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

Опубликована: Дек. 13, 2024

Abstract INTRODUCTION Progressive supranuclear palsy (PSP) is a devastating 4R tauopathy affecting motor functions and often misdiagnosed/underdiagnosed due to lack of specific biomarkers. Synaptic loss an eminent feature tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB‐J holds great potential for early diagnosis; however, there substantial knowledge gap in terms the mechanism extent nature METHODS Here, we report in‐depth post mortem validation mechanistic study PSP control brains using radioligand/autoradiography binding studies, alongside biochemical correlation analyses markers. RESULTS AND DISCUSSION 3 H‐UCB‐J targeted vesicle protein 2A with high specificity demonstrated distinct interrelation markers patients’ brain regions. The severely affected globus pallidus revealed deficits glutamate/GABAergic terminals. Cortical subcortical tau load differentially impacted marker profiles across patients, warranting further investigation. Highlights progressive conserved single nM site different depicted prominent at synaptosome levels terminals as compared control. distinctly influenced profile patients highlighted that presynaptic “ubiquitous” individually might not be able represent complete state deficits/loss brains.

Язык: Английский

Процитировано

0