Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [11C]MPC‐6827 PET imaging in rodent models of Alzheimer's‐related pathology DOI Creative Commons

Naresh Damuka,

Riley E. Irmen,

Ivan Krizan

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6082 - 6093

Published: July 5, 2024

Abstract INTRODUCTION Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation critical connecting amyloid beta (Aβ) and tau‐based degenerative events early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT‐PET radiotracer, [ 11 C]MPC‐6827, multiple established AD mouse models. METHODS Longitudinal PET, biodistribution, autoradiography, immunohistochemistry, behavioral studies were conducted at time points APPswe/PSEN1dE9 (APP/PS1), P301S‐PS19 (P301S), 5xFAD, age‐matched control mice. RESULTS C]MPC‐6827 brain showed significant increases APP/PS1, P301S, 5xFAD mice compared to controls. correlated positively with immunohistochemistry results negatively behavior data. DISCUSSION Our study demonstrated longitudinal PET models the first time. Strong correlations between biomarker data underscored interplay destabilization, amyloid, tau pathology AD. These suggest as a promising tool monitoring progression. Highlights using (AD) revealed an onset microtubule dysregulation, radiotracer uptake evident from 2 4 months age. Intra‐group analysis progressive increase increasing burden, supported by molecular pathological markers. its efficacy detecting alterations preceding observable models, suggesting potential imaging. The inclusion model further elucidated impact toxicity on inducing hyperphosphorylation‐mediated highlighting versatility delineating various aspects pathology. provides immediate clarity high microtubule‐based brains setting, which directly informs clinical utility Aβ/tau‐based studies.

Language: Английский

Radiation-induced brain injury in non-human primates: A dual tracer PET study with [11C]MPC-6827 and [11C]PiB DOI Creative Commons

Naresh Damuka,

George W. Schaaf,

Mack Miller

et al.

Neuroimage Reports, Journal Year: 2025, Volume and Issue: 5(1), P. 100245 - 100245

Published: Feb. 19, 2025

Language: Английский

Citations

1
Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [11C]MPC‐6827 PET imaging in rodent models of Alzheimer's‐related pathology DOI Creative Commons

Naresh Damuka,

Riley E. Irmen,

Ivan Krizan

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6082 - 6093

Published: July 5, 2024

Abstract INTRODUCTION Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation critical connecting amyloid beta (Aβ) and tau‐based degenerative events early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT‐PET radiotracer, [ 11 C]MPC‐6827, multiple established AD mouse models. METHODS Longitudinal PET, biodistribution, autoradiography, immunohistochemistry, behavioral studies were conducted at time points APPswe/PSEN1dE9 (APP/PS1), P301S‐PS19 (P301S), 5xFAD, age‐matched control mice. RESULTS C]MPC‐6827 brain showed significant increases APP/PS1, P301S, 5xFAD mice compared to controls. correlated positively with immunohistochemistry results negatively behavior data. DISCUSSION Our study demonstrated longitudinal PET models the first time. Strong correlations between biomarker data underscored interplay destabilization, amyloid, tau pathology AD. These suggest as a promising tool monitoring progression. Highlights using (AD) revealed an onset microtubule dysregulation, radiotracer uptake evident from 2 4 months age. Intra‐group analysis progressive increase increasing burden, supported by molecular pathological markers. its efficacy detecting alterations preceding observable models, suggesting potential imaging. The inclusion model further elucidated impact toxicity on inducing hyperphosphorylation‐mediated highlighting versatility delineating various aspects pathology. provides immediate clarity high microtubule‐based brains setting, which directly informs clinical utility Aβ/tau‐based studies.

Language: Английский

Citations

2