Abstract TMP114: Cerebral Ischemia Combined With Amyloid Angiopathy Significantly Deteriorated Cognitive Impairment via Angiotensin AT1 Receptor in a Mouse Model of Alzheimer’s Disease

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Takashi Nakagawa ◽  
Yu Hasegawa ◽  
Shokei K Mitsuyama
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Cognitive Decline ◽  
Escape Latency ◽  
Amyloid Angiopathy ◽  
Wild Type ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mouse

Introduction: Ischemic stroke is suggested to be potentially associated with cognitive impairment in Alzheimer’s disease. Recent clinical data suggest that treatment with angiotensin receptor blocker (ARB) is associated with less incidence of Alzheimer’s disease than other classes of antihypertensive drugs. However, it is unknown whether cerebral ischemia can indeed trigger cognitive decline in Alzheimer’s disease and whether ARB can exert beneficial effect on ischemia-induced cognitive decline. Hypothesis: We hypothesized that cerebral ischemia deteriorates cognitive impairment in Alzheimer’s disease, through angiotensin II. Methods and results: We used 5XFAD mouse, a model of Alzheimer’s disease with vascular and cerebral amyloid-β(Aβ) deposition. Transient cerebral ischemia of mice was induced by bilateral common carotid artery occlusion (BCCAO) for 17 minutes. The post-treatment with olmesartan, an ARB, or vehicle was started at 24 hours after BCCAO, and was performed for 5 weeks. Mice were divided into 5 groups: (1) wild type, (2) wild type with BCCAO, (3) 5XFAD, (4) 5XFAD with BCCAO, (5) 5XFAD with BCCAO and olmesartan administration, to evaluate cognitive impairment. BCCAO in 5XFAD caused greater escape latency (p<0.01) on Water maze test (reference-/working-memory) and greater migration distance (p<0.05) on Open field test than that in wild type, indicating that cerebral ischemia combined with Aβ deposition enhanced cognitive decline. Post-treatment with olmesartan significantly reduced escape latency (p<0.01) on Water maze test, retention trial latency (p<0.05) on Passive avoidance test, and retention time of outer zone (p<0.01) on Open field test in 5XFAD subjected to BCCAO. BCCAO significantly deteriorated cognitive impairment, and this protection against BCCAO by olmesartan was associated with the protection of neuron in hippocampus and the suppression of blood-brain barrier disruption. Furthermore, olmesartan significantly attenuated brain oxidative stress, and NADPH oxidase subunits P67 in 5XFAD. Conclusion: We first demonstrated that cerebral ischemia combined with amyloid angiopathy markedly deteriorates cognitive impairment in 5XFAD mouse, through AT1 receptor.

Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer's disease

Life Sciences ◽  
2011 ◽  
Vol 89 (3-4) ◽  
pp. 86-92 ◽  
Author(s):  
Jing Li ◽  
Yan-Jiang Wang ◽  
Meng Zhang ◽  
Chuan-Qin Fang ◽  
Hua-Dong Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cerebral Ischemia ◽  
Rat Model ◽  
Model Of Alzheimer’S Disease

scholarly journals ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease

2020 ◽  
Vol 139 (3) ◽  
pp. 485-502 ◽  
Author(s):  
Charles E. Evans ◽  
James S. Miners ◽  
Giulia Piva ◽  
Christine L. Willis ◽  
David M. Heard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Animal Models ◽  
Cognitive Decline ◽  
Intraperitoneal Administration ◽  
Tg2576 Mouse ◽  
Model Of Alzheimer’S Disease ◽  
Increased Risk ◽  
Tg2576 Mice

Abstract Mid-life hypertension and cerebrovascular dysfunction are associated with increased risk of later life dementia, including Alzheimer’s disease (AD). The classical renin–angiotensin system (cRAS), a physiological regulator of blood pressure, functions independently within the brain and is overactive in AD. cRAS-targeting anti-hypertensive drugs are associated with reduced incidence of AD, delayed onset of cognitive decline, and reduced levels of Aβ and tau in both animal models and human pathological studies. cRAS activity is moderated by a downstream regulatory RAS pathway (rRAS), which is underactive in AD and is strongly associated with pathological hallmarks in human AD, and cognitive decline in animal models of CNS disease. We now show that enhancement of brain ACE2 activity, a major effector of rRAS, by intraperitoneal administration of diminazene aceturate (DIZE), an established activator of ACE2, lowered hippocampal Aβ and restored cognition in mid-aged (13–14-month-old) symptomatic Tg2576 mice. We confirmed that the protective effects of DIZE were directly mediated through ACE2 and were associated with reduced hippocampal soluble Aβ42 and IL1-β levels. DIZE restored hippocampal MasR levels in conjunction with increased NMDA NR2B and downstream ERK signalling expression in hippocampal synaptosomes from Tg2576 mice. Chronic (10 weeks) administration of DIZE to pre-symptomatic 9–10-month-old Tg2576 mice, and acute (10 days) treatment in cognitively impaired 12–13-month-old mice, prevented the development of cognitive impairment. Together these data demonstrate that ACE2 enhancement protects against and reverses amyloid-related hippocampal pathology and cognitive impairment in a preclinical model of AD.

scholarly journals Age-related changes in social behaviours in the 5xFAD mouse model of Alzheimer’s disease

2018 ◽  
Author(s):  
Filip Kosel ◽  
Paula Torres Munoz ◽  
J. Renee Yang ◽  
Aimee A. Wong ◽  
Tamara B. Franklin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Social Interactions ◽  
Scent Marking ◽  
Wild Type ◽  
Social Investigation ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
5Xfad Mouse

AbstractIn addition to memory impairments, patients with Alzheimer’s disease (AD) exhibit a number of behavioural and psychological symptoms that can affect social interactions over the course of the disease. While altered social interactions have been demonstrated in a number of mouse models of AD, many models only recapitulate the initial stages of the disease, and these behavioural changes have yet to be examined over the course of disease progression. By performing a longitudinal study using the 5xFAD mouse model, we have demonstrated that transgenic females exhibit progressive alterations in social investigation compared to wild-type controls. Transgenic females exhibited an age-related reduction in interest for social odours, as well as reduced investigative behaviours towards novel conspecifics in a novel environment. However, transgenic mice exhibited no obvious olfactory deficits, nor any changes in scent-marking behaviour compared to wild-type controls, indicating that changes in investigative behaviour were due to motivation to engage with a social stimulus. This evidence suggests that transgenic 5xFAD females exhibit increased social anxiety in novel environments compared to wildtype controls. Overall, transgenic 5xFAD female mice mimic some features of social withdrawal observed in human AD patients suggesting this strain may be suitable for modelling aspects of the social dysfunction observed in human patients.

Evidence for Early Cognitive Impairment Related to Frontal Cortex in the 5XFAD Mouse Model of Alzheimer's Disease

2013 ◽  
Vol 33 (3) ◽  
pp. 781-796 ◽  
Author(s):  
Stéphane D. Girard ◽  
Kévin Baranger ◽  
Cyrielle Gauthier ◽  
Marlyse Jacquet ◽  
Anne Bernard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Frontal Cortex ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mouse

scholarly journals Altered Brain Adiponectin Receptor Expression in the 5XFAD Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 13 (7) ◽  
pp. 150 ◽  
Author(s):  
Anishchal A. Pratap ◽  
R. M. Damian Holsinger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Receptor Expression ◽  
Wild Type ◽  
Model Of Alzheimer’S Disease ◽  
Activated State ◽  
5Xfad Mouse ◽  
Neuronal Expression ◽  
The Brain

Metabolic syndromes share common pathologies with Alzheimer’s disease (AD). Adiponectin, an adipocyte-derived protein, regulates energy metabolism via its receptors, AdipoR1 and AdipoR2. To investigate the distribution of adiponectin receptors (AdipoRs) in Alzheimer’s, we examined their expression in the aged 5XFAD mouse model of AD. In age-matched wild-type mice, we observed neuronal expression of both ARs throughout the brain as well as endothelial expression of AdipoR1. The pattern of receptor expression in the aged 5XFAD brain was significantly perturbed. Here, we observed decreased neuronal expression of both ARs and decreased endothelial expression of AdipoR1, but robust expression of AdipoR2 in activated astrocytes. We also observed AdipoR2-expressing astrocytes in the dorsomedial hypothalamic and thalamic mediodorsal nuclei, suggesting the possibility that astrocytes utilise AdipoR2 signalling to fuel their activated state in the AD brain. These findings provide further evidence of a metabolic disturbance and demonstrate a potential shift in energy utilisation in the AD brain, supporting imaging studies performed in AD patients.

Subjective Spatial Navigation Complaints - A Frequent Symptom Reported by Patients with Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer's Disease

2018 ◽  
Vol 15 (3) ◽  
pp. 219-228 ◽  
Author(s):  
Jiri Cerman ◽  
Ross Andel ◽  
Jan Laczo ◽  
Martin Vyhnalek ◽  
Zuzana Nedelska ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Spatial Navigation ◽  
Subjective Cognitive Decline ◽  
Great Effort ◽  
Frequent Symptom ◽  
Normal Controls

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

Sign in / Sign up

Export Citation Format

Share Document