scholarly journals Delta-secretase triggers Alzheimer’s disease pathologies in wild-type hAPP/hMAPT double transgenic mice

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Zhourui Wu ◽  
Xia Liu ◽  
Liming Cheng ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Senile Plaques ◽  
Wild Type ◽  
Double Transgenic Mouse ◽  
Double Transgenic Mice ◽  
One Year ◽  
Aβ Production ◽  
Human Wild Type

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aβ containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Aβ production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of δ-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, δ-secretase facilitates AD pathogenesis independent of any patient-derived mutation.

scholarly journals Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

2020 ◽  
Vol 21 (3) ◽  
pp. 1133 ◽  
Author(s):  
Baruh Polis ◽  
Kolluru D. Srikanth ◽  
Vyacheslav Gurevich ◽  
Naamah Bloch ◽  
Hava Gil-Henn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Adult Neurogenesis ◽  
Progenitor Cell ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Number ◽  
Wild Type ◽  
Newborn Neuron

Adult neurogenesis is a complex physiological process, which plays a central role in maintaining cognitive functions, and consists of progenitor cell proliferation, newborn cell migration, and cell maturation. Adult neurogenesis is susceptible to alterations under various physiological and pathological conditions. A substantial decay of neurogenesis has been documented in Alzheimer’s disease (AD) patients and animal AD models; however, several treatment strategies can halt any further decline and even induce neurogenesis. Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. To better evaluate this effect, we chronically administered an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and applied an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy. Remarkably, we evidenced a significant reduction in the density of neuronal progenitors, which demonstrate a different phenotype in the hippocampi of triple-transgenic mice as compared to wild-type animals. However, norvaline showed no significant effect upon the progenitor cell number and constitution. We demonstrated that norvaline treatment leads to an escalation of the polysialylated neuronal cell adhesion molecule immunopositivity, which suggests an improvement in the newborn neuron survival rate. Additionally, we identified a significant increase in the hippocampal microtubule-associated protein 2 stain intensity. We also explore the molecular mechanisms underlying the effects of norvaline on adult mice neurogenesis and provide insights into their machinery.

P1-080: STUDY OF DAILY ORAL GENISTEIN ON SPATIAL AND OLFACTORY MEMORY IN WILD TYPE AND TRANSGENIC MICE THAT MODEL ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_5) ◽  
pp. P301-P302
Author(s):  
Alyson C. Williamson ◽  
Hayley R. LeBlanc ◽  
Brian G. Gentry ◽  
Craige C. Wrenn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Wild Type ◽  
Olfactory Memory

scholarly journals Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
T. Harach ◽  
N. Marungruang ◽  
N. Duthilleul ◽  
V. Cheatham ◽  
K. D. Mc Coy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Transgenic Mice ◽  
Intestinal Microbiota ◽  
Neurodegenerative Disorder ◽  
Wild Type ◽  
Germ Free ◽  
Amyloid Pathology ◽  
Aβ Amyloid

Abstract Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.

P1-108: Effects of space radiation on hippocampal-dependent learning and neuropathology in wild-type and Alzheimer's disease transgenic mice

2013 ◽  
Vol 9 ◽  
pp. P190-P190 ◽  
Author(s):  
Juliet Moncaster ◽  
Mark Wojnarowicz ◽  
Srikant Sarangi ◽  
Andrew Fisher ◽  
Olga Minaeva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Space Radiation ◽  
Wild Type ◽  
Dependent Learning

APP Transgenic Mice Tg2576 Accumulate Aβ Peptides That Are Distinct from the Chemically Modified and Insoluble Peptides Deposited in Alzheimer's Disease Senile Plaques†

Biochemistry ◽  
2002 ◽  
Vol 41 (3) ◽  
pp. 922-928 ◽  
Author(s):  
Walter Kalback ◽  
M. Desiree Watson ◽  
Tyler A. Kokjohn ◽  
Yu-Min Kuo ◽  
Nicole Weiss ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Senile Plaques ◽  
Aβ Peptides ◽  
Chemically Modified

scholarly journals Deposition of BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Gang Luo ◽  
Hongxia Xu ◽  
Yinuo Huang ◽  
Dapeng Mo ◽  
Ligang Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Protein Expression ◽  
Protein Accumulation ◽  
Significant Difference ◽  
Abnormal Accumulation ◽  
Double Transgenic Mice ◽  
Bace 1

The main causes of Alzheimer’s disease remain elusive. Previous data have implicated the BACE-1 protein as a central player in the pathogenesis of Alzheimer’s disease. However, many inhibitors of BACE-1 have failed during preclinical and clinical trials for AD treatment. Therefore, uncovering the exact role of BACE-1 in AD may have significant impact on the future development of therapeutic agents. Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains of mice here. Immunofluorescence, immunohistochemistry, and western blot were performed to measure the distributing pattern and expression level of BACE-1. We found obvious BACE-1 protein accumulation in 3-month-old APP/PS1 mice, which had increased by the time of 6 months. Coimmunostaining results showed BACE-1 surrounded amyloid plaques in brain sections. The abnormal protein expression might not be attributable to the upregulation of BACE-1 protein, as no significant difference of protein expression was observed between wild-type and APP/PS1 mice. With antibodies against BACE-1 and CD31, we found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels. The aberrant distribution of BACE-1 in APP/PS1 mice suggests BACE-1 may be involved in the microvascular abnormality of AD.

Effect of Plant Compound Curcumin on the Expression of a-Synuclein in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

2013 ◽  
Vol 781-784 ◽  
pp. 643-646
Author(s):  
Xiao Lin ◽  
Li Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Dependent Manner ◽  
Double Transgenic Mice ◽  
Ad Alzheimer’S Disease ◽  
Dose Dependent

In this study, we aim to investigate the effect of curcumin on the expression of a-synuclein in the APPswe/PS1dE9 double transgenic mice. APPswe/PS1dE9 double transgenic mice were used as AD (Alzheimer's disease) model and fed with different concentrations of curcumin every day for 6 months, then immunohistochemistry method were used to detect the expression of a-synuclein in hippocampus of mice. The expression of a-syn in hippocampal neuron was decreased significantly after treated with 0.16g/kg to 1.0g/kg curcumin, the change was apparent in dose-dependent manner (P<0.05). a-synuclein pay an important role in the genesis and development of Alzheimer's disease and decreased level of a-synuclein might contribute to the neuroprotective effect of Curcumin, which may become a new target for the prevention and treatment of Alzheimer's disease.

Sign in / Sign up

Export Citation Format

Share Document