Immunization with Aβ3-10-KLH vaccine improves cognitive function and ameliorates mitochondrial dysfunction and reduces Alzheimer’s disease-like pathology in Tg-APPswe/PSEN1dE9 mice

2021 ◽  
Author(s):  
Xiao-Yi Zhang ◽  
Meng Yuan ◽  
Xue-Jing Yan ◽  
Shuo Liu ◽  
Guo-Qing Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction

scholarly journals Role of RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer's Disease

2021 ◽  
Author(s):  
Sanjay Awasthi ◽  
Ashly Hindle ◽  
Neha Sawant ◽  
Mathew George ◽  
Murali Vijayan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Sensory Function ◽  
Expression Of Genes

The purpose of our study is to understand the role of the Ralbp1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer's disease (AD) pathogenesis. The Ralbp1 gene encodes the 76 kDa protein Rlip (aka RLIP76). Previous studies have revealed its role in OS-related cancer. However, Rlip is transcriptionally regulated by EP300, a CREB-binding protein that is important for synaptic plasticity in the brain. Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. OS causes rapid cellular accumulation of Rlip and its translocation from a tubulin-bound complex to the plasma membrane, mitochondria and nucleus. Therefore, Rlip may play an important role in maintaining cognitive function in the face of OS-related injury. This study is aimed to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype and Rlip+/- mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in mouse brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, inhibition of stress-activated gene expression, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues of these mice. Furthermore, we compared the cognitive function of wildtype and Rlip+/- mice. Behavioral, basic motor and sensory function tests in Rlip+/- mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function, and CREB signaling genes in the Rlip+/- mouse liver. Our results suggest that the Rlip deficiency-associated increase in OS and mitochondrial dysfunction could contribute to the development of OS-related AD processes. Therefore, the restoration of Rlip activity and endogenous cytoprotective mechanisms by pharmacological interventions is a novel approach to protect against AD.

scholarly journals RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3113
Author(s):  
Sanjay Awasthi ◽  
Ashly Hindle ◽  
Neha A. Sawant ◽  
Mathew George ◽  
Murali Vijayan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Gene Networks ◽  
Sensory Function ◽  
Expression Of Genes ◽  
The Impact

The purpose of our study is to understand the role of the RALBP1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The RALPB1 gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. We hypothesized that Rlip may play an important role in maintaining cognitive function. The aim of this study is to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype (WT) and Rlip+/− mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, stress response, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues from these mice. Furthermore, we compared the cognitive function of WT and Rlip+/− mice. Behavioral, basic motor and sensory function tests in Rlip+/− mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function and CREB signaling genes in the Rlip+/− mouse brain. Our results suggest that Rlip deficiency-associated increases in OS and mitochondrial dysfunction could contribute to the development or progression of OS-related AD processes.

Development and Evaluation of a Tactile Cognitive Function Test Device for Alzheimer’s Disease Early Detection

2015 ◽  
Vol 3 (2) ◽  
pp. 58-65 ◽  
Author(s):  
Jiajia Yang ◽  
Mohd Usairy Syafiq ◽  
Yinghua Yu ◽  
Satoshi Takahashi ◽  
Zhenxin Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Early Detection ◽  
Test Device ◽  
Function Test ◽  
Cognitive Function Test

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Virtual Reality-Based Cognitive Stimulation on People with Mild to Moderate Dementia due to Alzheimer’s Disease: A Pilot Randomized Controlled Trial

2021 ◽  
Vol 18 (10) ◽  
pp. 5290
Author(s):  
Jorge Oliveira ◽  
Pedro Gamito ◽  
Teresa Souto ◽  
Rita Conde ◽  
Maria Ferreira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Controlled Trial ◽  
Virtual Reality ◽  
Cognitive Function ◽  
Controlled Trial ◽  
Cognitive Stimulation ◽  
Randomized Controlled ◽  
Moderate Dementia ◽  
Pilot Randomized Controlled Trial

The use of ecologically oriented approaches with virtual reality (VR) depicting instrumental activities of daily living (IADL) is a promising approach for interventions on acquired brain injuries. However, the results of such an approach on dementia caused by Alzheimer’s disease (AD) are still lacking. This research reports on a pilot randomized controlled trial that aimed to explore the effect of a cognitive stimulation reproducing several IADL in VR on people with mild-to-moderate dementia caused by AD. Patients were recruited from residential care homes of Santa Casa da Misericórdia da Amadora (SCMA), which is a relevant nonprofit social and healthcare provider in Portugal. This intervention lasted two months, with a total of 10 sessions (two sessions/week). A neuropsychological assessment was carried out at the baseline and follow-up using established neuropsychological instruments for assessing memory, attention, and executive functions. The sample consisted of 17 patients of both genders randomly assigned to the experimental and control groups. The preliminary results suggested an improvement in overall cognitive function in the experimental group, with an effect size corresponding to a large effect in global cognition, which suggests that this approach is effective for neurocognitive stimulation in older adults with dementia, contributing to maintaining cognitive function in AD.

scholarly journals Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction

2021 ◽  
pp. 1-16
Author(s):  
Wei Wei ◽  
Yinghua Liu ◽  
Chunling Dai ◽  
Narjes Baazaoui ◽  
Yunn-Chyn Tung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Early Development ◽  
Neurodegenerative Disorder ◽  
Synaptic Dysfunction ◽  
Early Postnatal Development ◽  
Wild Type Female

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction. Objective: To explore strategies for early intervention to prevent Alzheimer’s disease. Methods: In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated. Results: P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice. Conclusion: These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

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