scholarly journals Brain Cellular Senescence in Mouse Models of Alzheimer's Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 937-937
Author(s):  
Ruben Riordan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Cellular Senescence ◽  
Cognitive Deficits ◽  
Matched Control ◽  
Wild Type ◽  
Expected Time ◽  
Do So

Abstract The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild type mice as well as in Alzheimer’s disease (AD) models. AD models recapitulate some, but not all components of disease and do so at different rates. Whether brain cellular senescence is recapitulated in some or all AD models, and whether the emergence of cellular senescence in AD mouse models occurs before or after the expected onset of AD-like cognitive deficits in these models is not yet known. The goal of this study was to identify mouse models of AD and AD-related dementias that develop measurable markers of cellular senescence in brain and thus may be useful to study the role of cellular senescence in these conditions. We measured levels of cellular senescence markers in brains of P301S(PS19), P301L, hTau, and 3xTg-AD mice that model amyloidopathy and/or tauopathy in AD and related dementias, and in wild type, age-matched control mice for each strain. Expression of cellular senescence markers in brains of transgenic P301L and 3xTg-AD mice was largely indistinguishable from that in WT control age-matched mice. In contrast, markers of cellular senescence were significantly increased in brains of transgenic P301S and hTau mice as compared to WT control mice at the expected time of onset of AD-like cognitive deficits. Taken together, our data suggest that P301S(PS19) and hTau mice may be useful for the study of brain cellular senescence in tauopathies including, but not limited to, AD.

scholarly journals Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis

eNeuro ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. ENEURO.0025-17.2017 ◽  
Author(s):  
Denise Isabelle Briggs ◽  
Erwin Defensor ◽  
Pooneh Memar Ardestani ◽  
Bitna Yi ◽  
Michelle Halpain ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Learning And Memory ◽  
Mouse Models ◽  
Memory Impairment

scholarly journals TRANSGENIC MOUSE MODELS OF ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S835-S835
Author(s):  
Charnae A Henry-Smith ◽  
Xianlin Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Myelin Sheath ◽  
Thinking Skills ◽  
Drug Dosage ◽  
Whole Body ◽  
To Receive ◽  
The Brain

Abstract Alzheimer’s disease is a progressive brain disease that slowly destroys memory and thinking skills. Alzheimer’s is characterized by an increase in Aβ plaques , and tau tangles. Neurons in the brain have axons covered in myelin sheath that connect microglia and astrocytes. The myelin sheath is composed of about 70% lipid composition; Sulfatide contributing to 30% overall. Sulfatide changes the morphology of primary microglia to their activated form. To study the role of microglia activation and sulfatide levels, three different mouse models were created: APP KI mice, CST Whole Body Ko mice, and cCST (conditional) KO. In order to create the genotype of the APP KI mice, a breeding mouse line was created. The APP KI gene had to be introduced in Plp1-Cre and cCST KO crossed mice to receive a working mouse model. During the duration of breeding for the APP KI mice, a preliminary experiment was performed on the CST KO mice. These mice were given the PLX3397 diet with the aim to remove the microglia and to see the effect of Aβ plaques. The PLX3397 will reduce the microglia targeting the CSF1R. After consuming the diet, the mice were harvested to collect tissues from the brain and spinal cord. Lipidomics and immunohistology were performed. In conclusion, we will continue the breeding of the CST flox/flox / Plp1-Cre / APP KI mice, and the drug dosage and treatment to be used in our APP KI mice will be based on preliminary data from our CST mice.

scholarly journals TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

2015 ◽  
Vol 212 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Taylor R. Jay ◽  
Crystal M. Miller ◽  
Paul J. Cheng ◽  
Leah C. Graham ◽  
Shane Bemiller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Mouse Models ◽  
Myeloid Cells ◽  
Cell Types ◽  
Targeted Therapeutics ◽  
Amyloid Deposits ◽  
Inflammatory Macrophages

Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2’s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2+ macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.

scholarly journals Does Chronic Sleep Fragmentation Lead to Alzheimer's Disease in Young Wild-Type Mice?

2021 ◽  
Vol 13 ◽  
Author(s):  
Li Ba ◽  
Lifang Huang ◽  
Ziyu He ◽  
Saiyue Deng ◽  
Yi Xie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glucose Metabolism ◽  
Differential Expression ◽  
Mouse Models ◽  
Neurological Diseases ◽  
Expression Patterns ◽  
Sleep Fragmentation ◽  
Wild Type ◽  
Chronic Sleep

Chronic sleep insufficiency is becoming a common issue in the young population nowadays, mostly due to life habits and work stress. Studies in animal models of neurological diseases reported that it would accelerate neurodegeneration progression and exacerbate interstitial metabolic waste accumulation in the brain. In this paper, we study whether chronic sleep insufficiency leads to neurodegenerative diseases in young wild-type animals without a genetic pre-disposition. To this aim, we modeled chronic sleep fragmentation (SF) in young wild-type mice. We detected pathological hyperphosphorylated-tau (Ser396/Tau5) and gliosis in the SF hippocampus. 18F-labeled fluorodeoxyglucose positron emission tomography scan (18F-FDG-PET) further revealed a significant increase in brain glucose metabolism, especially in the hypothalamus, hippocampus and amygdala. Hippocampal RNAseq indicated that immunological and inflammatory pathways were significantly altered in 1.5-month SF mice. More interestingly, differential expression gene lists from stress mouse models showed differential expression patterns between 1.5-month SF and control mice, while Alzheimer's disease, normal aging, and APOEε4 mutation mouse models did not exhibit any significant pattern. In summary, 1.5-month sleep fragmentation could generate AD-like pathological changes including tauopathy and gliosis, mainly linked to stress, as the incremented glucose metabolism observed with PET imaging suggested. Further investigation will show whether SF could eventually lead to chronic neurodegeneration if the stress condition is prolonged in time.

Assessing Sex-Specific Circadian, Metabolic, and Cognitive Phenotypes in the AβPP/PS1 and APPNL - F/NL - F Models of Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jesse Britz ◽  
Emmanuel Ojo ◽  
Asmita Dhukhwa ◽  
Takashi Saito ◽  
Takaomi C. Saido ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Cognitive Deficits ◽  
Activity Patterns ◽  
Spatial Learning And Memory ◽  
Plaque Pathology ◽  
Glucose Sensitivity ◽  
Old Females ◽  
Daily Activity Patterns

Background: Circadian disruption has long been recognized as a symptom of Alzheimer’s disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits. Objective: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL - F/NL - F) AD mouse models from the period of plaque initiation (6 months) through 12 months. Methods: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed. A comparison was made across sexes. Results: Sex-dependent hyperactivity in AβPP/PS1 mice was observed. In comparison to C57BL/6J animals, 6-month-old male AβPP/PS1 demonstrated nighttime hyperactivity, as did 12-month-old females. Female AβPP/PS1 animals performed significantly worse on a MWM task than AβPP/PS1 males at 12 months and trended toward increased plaque pathology. APPNL - F/NL - F 12-month-old males performed significantly worse on the MWM task compared to 12-month-old females. Significantly greater plaque pathology occurred in AβPP/PS1 animals as compared to APPNL - F/NL - F animals. Female AβPP/PS1 animals performed significantly worse than APPNL - F/NL - F animals in spatial learning and memory tasks, though this was reversed in males. Conclusion: Taken together, this study provides novel insights into baseline sex differences, as well as characterizes baseline diurnal activity variations, in the AβPP/PS1 and APPNL - F/NL - F AD mouse models.

Possible Role of Dynorphins in Alzheimer's Disease and Age-Related Cognitive Deficits

2013 ◽  
Vol 13 (2-3) ◽  
pp. 82-85 ◽  
Author(s):  
Caroline Ménard ◽  
Herbert Herzog ◽  
Christoph Schwarzer ◽  
Rémi Quirion
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Age Related

scholarly journals Neuronal and Astrocytic Extracellular Vesicle Biomarkers in Blood Reflect Brain Pathology in Mouse Models of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 993
Author(s):  
Francheska Delgado-Peraza ◽  
Carlos J. Nogueras-Ortiz ◽  
Olga Volpert ◽  
Dong Liu ◽  
Edward J. Goetzl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Extracellular Vesicle ◽  
Strong Correlations ◽  
Wild Type ◽  
Total Tau ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Potential Use

Circulating neuronal extracellular vesicles (NEVs) of Alzheimer’s disease (AD) patients show high Tau and β-amyloid (Aβ) levels, whereas their astrocytic EVs (AEVs) contain high complement levels. To validate EV proteins as AD biomarkers, we immunocaptured NEVs and AEVs from plasma collected from fifteen wild type (WT), four 2xTg-AD, nine 5xFAD, and fifteen 3xTg-AD mice and assessed biomarker relationships with brain tissue levels. NEVs from 3xTg-AD mice had higher total Tau (p = 0.03) and p181-Tau (p = 0.0004) compared to WT mice. There were moderately strong correlations between biomarkers in NEVs and cerebral cortex and hippocampus (total Tau: cortex, r = 0.4, p = 0.009; p181-Tau: cortex, r = 0.7, p < 0.0001; hippocampus, r = 0.6, p < 0.0001). NEVs from 5xFAD compared to other mice had higher Aβ42 (p < 0.005). NEV Aβ42 had moderately strong correlations with Aβ42 in cortex (r = 0.6, p = 0.001) and hippocampus (r = 0.7, p < 0.0001). AEV C1q was elevated in 3xTg-AD compared to WT mice (p = 0.005); AEV C1q had moderate-strong correlations with C1q in cortex (r = 0.9, p < 0.0001) and hippocampus (r = 0.7, p < 0.0001). Biomarkers in circulating NEVs and AEVs reflect their brain levels across multiple AD mouse models supporting their potential use as a “liquid biopsy” for neurological disorders.

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