Maresin-like 1 Ameliorates Neuropathology of Alzheimer’s Disease in Brains of a Transgenic Mouse Model DOI Creative Commons
Pallavi Shrivastava, Yan Lü, Shanchun Su

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2865 - 2865

Published: Dec. 17, 2024

(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis Alzheimer’s disease (AD); consequently, resolving is pivotal amelioration AD pathology. This can potentially be achieved by treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. (2) Methods: Here, we report histological effects long-term an SPM, maresin-like 1 (MarL1), on a transgenic 5xFAD mouse model. (3) Results: MarL1 reduced Aβ overload, curbed loss neurons brains especially cholinergic associated cleaved-caspase-3-associated apoptotic degeneration, microgliosis and pro-inflammatory M1 polarization microglia, AD-associated decline anti-inflammatory Iba1+Arg-1+-M2 inhibited phenotypic switching N1 neutrophils, promoted blood–brain barrier-associated tight-junction protein claudin-5 decreased neutrophil leakage brains, induced switch neutrophils toward inflammation-resolving N2 phenotype. (4) Conclusions: Long-term administration mitigates AD-related neuropathogenesis curbing neurodegeneration, based results. These findings provide preclinical leads mechanistic insights for development into effective modality ameliorate pathogenesis.

Language: Английский

Updates on mouse models of Alzheimer’s disease DOI Creative Commons

Michael Z Zhong,

Thomas Peng,

Mariana Lemos Duarte

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 11, 2024

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative in United States (US). Animal models, specifically mouse models have been developed to better elucidate mechanisms and test therapeutic strategies for AD. A large portion of effort field was focused on developing transgenic (Tg) through over-expression genetic mutations associated with familial AD (FAD) patients. Newer generations knock-in (KI)/knock-out (KO) or CRISPR gene editing technologies, both sporadic risk genes hope more accurately model proteinopathies without human brains. In this review, we summarized phenotypes a few commonly used as well newly translational research laboratories including presence absence key pathological features such amyloid tau pathology, synaptic neuronal degeneration cognitive behavior deficits. addition, advantages limitations these elaborated along discussions any sex-specific features. More importantly, omics data from available analyzed categorize molecular signatures each reminiscent brain changes, guide future selection suitable specific questions be addressed field.

Language: Английский

Citations

45
Characterizing molecular and synaptic signatures in mouse models of late‐onset Alzheimer's disease independent of amyloid and tau pathology DOI Creative Commons
Kevin P. Kotredes, Ravi S. Pandey, Scott C. Persohn

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(6), P. 4126 - 4146

Published: May 12, 2024

Abstract INTRODUCTION MODEL‐AD (Model Organism Development and Evaluation for Late‐Onset Alzheimer's Disease) is creating distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory progression of late‐onset disease (LOAD) more accurately. METHODS We created LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, humanized amyloid‐beta (Aβ). Mice were subjected a control diet or high‐fat/high‐sugar (LOAD2+HFD). assessed disease‐relevant outcome measures in plasma brain including neuroinflammation, Aβ, neurodegeneration, neuroimaging, multi‐omics. RESULTS By 18 months, LOAD2+HFD mice exhibited sex‐specific neuron loss, elevated insoluble Aβ42, increased neurofilament light chain (NfL), altered gene/protein expression related lipid metabolism synaptic function. Imaging showed reductions volume neurovascular uncoupling. Deficits acquiring touchscreen‐based cognitive tasks observed. DISCUSSION The comprehensive characterization reveals that this important preclinical studies seeking understand LOAD prior independent amyloid plaques tau tangles. Highlights unlike (e.g., fed diet, CD), presented subtle but significant loss neurons cortex, levels Ab42 brain, (NfL). Transcriptomics proteomics changes gene/proteins relating variety processes In vivo imaging revealed an age‐dependent reduction region (MRI) uncoupling (PET/CT). also demonstrated deficits acquisition tasks.

Language: Английский

Citations

8
Role of acute exposure to environmental stressors in the gut-brain-periphery axis in the presence of cognitive resilience DOI
Ruth Iban‐Arias, Ariana Soares Dias Portela,

Sibilla Masieri

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167760 - 167760

Published: March 2, 2025

Language: Английский

Citations

1
Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer’s disease research DOI Creative Commons
Alberto Granzotto, Bryce Vissel, Stefano L. Sensi

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Sept. 27, 2024

The recent, controversial approval of antibody-based treatments for Alzheimer’s disease (AD) is fueling a heated debate on the molecular determinants this condition. discussion should also incorporate critical revision limitations preclinical mouse models in advancing our understanding AD. We critically discuss animal models, stressing need careful consideration how experiments are designed and results interpreted. identify shortcomings AD to recapitulate complexity human disease. dissect these issues at quantitative, qualitative, temporal, context-dependent levels. argue that based oversimplistic assumptions proposed by amyloid cascade hypothesis (ACH) fail account multifactorial nature By shedding light constraints current experimental tools, review aims foster development implementation more clinically relevant tools. While we do not rule out role call alternative approaches be explored and, most importantly, re-evaluation ACH.

Language: Английский

Citations

4
Advancements and challenges in mouse models of Alzheimer’s disease DOI
Zhengjiang Qian, Yanjiao Li,

Keqiang Ye

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

4
Humanized rodent models of neurodegenerative diseases and other brain disorders DOI
X.B Zhang, Jianxiang Wang, Jiewen Zhang

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106112 - 106112

Published: March 1, 2025

Language: Английский

Citations

0
Involvement of Complement in Alzheimer’s Disease: From Genetics Through Pathology to Therapeutic Strategies DOI
Nikoleta Daskoulidou, Sarah M. Carpanini, Wioleta M. Zelek

et al.

Current topics in behavioral neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Maresin-like 1 Ameliorates Neuropathology of Alzheimer’s Disease in Brains of a Transgenic Mouse Model DOI Creative Commons
Pallavi Shrivastava, Yan Lü, Shanchun Su

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2865 - 2865

Published: Dec. 17, 2024

(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis Alzheimer’s disease (AD); consequently, resolving is pivotal amelioration AD pathology. This can potentially be achieved by treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. (2) Methods: Here, we report histological effects long-term an SPM, maresin-like 1 (MarL1), on a transgenic 5xFAD mouse model. (3) Results: MarL1 reduced Aβ overload, curbed loss neurons brains especially cholinergic associated cleaved-caspase-3-associated apoptotic degeneration, microgliosis and pro-inflammatory M1 polarization microglia, AD-associated decline anti-inflammatory Iba1+Arg-1+-M2 inhibited phenotypic switching N1 neutrophils, promoted blood–brain barrier-associated tight-junction protein claudin-5 decreased neutrophil leakage brains, induced switch neutrophils toward inflammation-resolving N2 phenotype. (4) Conclusions: Long-term administration mitigates AD-related neuropathogenesis curbing neurodegeneration, based results. These findings provide preclinical leads mechanistic insights for development into effective modality ameliorate pathogenesis.

Language: Английский

Citations

0