scholarly journals AGE-RELATED CHANGES IN MOTOR ABILITY AND MOTOR LEARNING IN TRIPLE TRANSGENIC (3×TG-AD) AND CONTROL (B6129SF1/J) MICE ON THE ACCELERATING ROTAROD

2013 ◽  
Vol 47 (2) ◽  
Author(s):  
Jonathan J. Oore ◽  
Leanne M. Fraser ◽  
Richard E. Brown
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Motor Learning ◽  
Learning Curve ◽  
Motor Ability ◽  
Cross Sectional ◽  
Award Winning ◽  
Age Related ◽  
Cross Sectional Design ◽  
And Control

Student Award-Winning PaperMouse models of Alzheimer’s disease (AD) show both cognitive and neuromotor impairments. We measured motor ability and motor learning of male and female triple transgenic (3×Tg-AD) and control (B6129SF1/J) mice on the accelerating Rotarod in a cross-sectional design at 2, 6, 9, 12, and 15 months of age. At all ages except for 2 months, transgenic mice performed better and had a steeper motor learning curve than controls. Female mice showed better motor performance than males, while males had a steeper learning curve than females. Age did not have a significant main effect on Rotarod performance. However, age and genotype showed an interaction, where the performance of 3×Tg-AD mice peaked at 6 months of age and decreased as age increased. The performance of controls was below that of 3×Tg-AD mice at each age. Behavioural differences seen in the 3×Tg-AD mice may help us to understand the development of neuromotor dysfunction in AD.Keywords: Alzheimer’s disease, Alzheimer models, Amyloid beta, motor ability, motor learning, Rotarod, tau, transgenic, 3×Tg-AD mice

scholarly journals Prevalence of Comorbidities in Individuals Diagnosed and Undiagnosed with Alzheimer’s Disease in León, Spain and a Proposal for Contingency Procedures to Follow in the Case of Emergencies Involving People with Alzheimer’s Disease

2020 ◽  
Vol 17 (10) ◽  
pp. 3398
Author(s):  
Macrina Tortajada-Soler ◽  
Leticia Sánchez-Valdeón ◽  
Marta Blanco-Nistal ◽  
José Alberto Benítez-Andrades ◽  
Cristina Liébana-Presa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Disorders ◽  
Cross Sectional Study ◽  
Control Group ◽  
Cross Sectional ◽  
Emergency Procedures ◽  
And Control ◽  
Similar Incidence

Background: Alzheimer’s disease (AD) which is the most common type of dementia is characterized by mental or cognitive disorders. People suffering with this condition find it inherently difficult to communicate and describe symptoms. As a consequence, both detection and treatment of comorbidities associated with Alzheimer’s disease are substantially impaired. Equally, action protocols in the case of emergencies must be clearly formulated and stated. Methods: We performed a bibliography search followed by an observational and cross-sectional study involving a thorough review of medical records. A group of AD patients was compared with a control group. Each group consisted of 100 people and were all León residents aged ≥65 years. Results: The following comorbidities were found to be associated with AD: cataracts, urinary incontinence, osteoarthritis, hearing loss, osteoporosis, and personality disorders. The most frequent comorbidities in the control group were the following: eye strain, stroke, vertigo, as well as circulatory and respiratory disorders. Comorbidities with a similar incidence in both groups included type 2 diabetes mellitus, glaucoma, depression, obesity, arthritis, and anxiety. We also reviewed emergency procedures employed in the case of an emergency involving an AD patient. Conclusions: Some comorbidities were present in both the AD and control groups, while others were found in the AD group and not in the control group, and vice versa.

scholarly journals Sex-specific interactions between procedural and deliberative decision-making systems in a mouse model of Alzheimer’s disease

2021 ◽  
Author(s):  
Rachel Anderson ◽  
Damyan W. Hart ◽  
Brian Sweis ◽  
Mathew A. Sherman ◽  
Mark J. Thomas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Decision Making ◽  
Mouse Model ◽  
Neural Substrates ◽  
Behavioral Changes ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Accurate Picture ◽  
And Control

AbstractA central question in aging and Alzheimer’s disease (AD) is when and how neural substrates underlying decision-making are altered. Here we show that while APP mice, a commonly used mouse model of AD, were able to learn Restaurant Row, a complex neuroeconomic decision-making task, they were significantly impaired in procedural, habit-forming, aspects of cognition and relied heavily on deliberation when making decisions. Surprisingly, these behavioral changes are associated with amyloid-beta (Aβ) pathology and network remodeling in the striatum, a key brain region involved in procedural cognition. Furthermore, APP mice and control mice relied on distinct sex-specific strategies in this neuroeconomic task. These findings provide foundational pillars to examine how aging and age-related neurodegenerative diseases impact decision-making across sexes. They also highlight the need for complex behavioral tasks that allow for the dissociation of competing neurally-distinct decision-making circuits to get an accurate picture of changes in neurodegenerative models of human disease.

scholarly journals Alzheimer’s Disease Caregiver Characteristics and Their Relationship with Anticipatory Grief

2021 ◽  
Vol 18 (16) ◽  
pp. 8838
Author(s):  
Alba Pérez-González ◽  
Josep Vilajoana-Celaya ◽  
Joan Guàrdia-Olmos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family Caregivers ◽  
Depressive Symptomatology ◽  
Anticipatory Grief ◽  
Cross Sectional ◽  
Sociodemographic Data ◽  
People With Dementia ◽  
Cross Sectional Design ◽  
Person With Dementia

In Alzheimer’s disease, two fundamental aspects become important for caregivers: ambiguity and ambivalence. Thus, anticipatory grief is considered an active psychological process that is very different from the mere anticipation of death. The present study aims to determine which characteristics of family caregivers of people with dementia, such as age, gender, educational level, relationship with the person with dementia, years with dementia or years as a caregiver, are related to the presence of anticipatory grief. A cross-sectional design was employed. The sample consisted of a total of 129 subjects who cared for a family member with dementia. A sociodemographic data sheet and a battery of tests measure the presence of anticipatory grief, caregiver burden and/or psychopathology. The results obtained allowed us to confirm some of the hypotheses regarding the anticipatory grief construct, the importance of the care time factor, in years and per day, as well as the relevance of the previous demographic and psychopathological profile (being female, spouse function and possible depressive symptomatology). Likewise, from the prediction analyzes performed, it seems that these variables can predict anticipatory grief. These results propose interesting opportunities to formulate care proposals to professionals and family caregivers in relation to care tasks and caregiver skills.

scholarly journals Deep Learning-Based Brain Transcriptomic Signatures Associated with the Neuropathological and Clinical Severity of Alzheimer's Disease

2021 ◽  
Author(s):  
Qi Wang ◽  
Benjamin Readhead ◽  
Kewei Chen ◽  
Yi Su ◽  
Eric M Reiman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Deep Learning ◽  
Temporal Cortex ◽  
Amyloid Β ◽  
Clinical Severity ◽  
Molecular Networks ◽  
Cross Sectional ◽  
Age Related ◽  
Gene Modules

Brain tissue gene expression from donors with and without Alzheimer's disease (AD) have been used to help inform the molecular changes associated with the development and potential treatment of this disorder. Here, we use a deep learning method to analyze RNA-seq data from 1,114 brain donors from the AMP-AD consortium to characterize post-mortem brain transcriptome signatures associated with amyloid-β plaque, tau neurofibrillary tangles, and clinical severity in multiple AD dementia populations. Starting from the cross-sectional data in the ROSMAP cohort (n = 634), a deep learning framework was built to obtain a trajectory that mirrors AD progression. A severity index (SI) was defined to quantitatively measure the progression based on the trajectory. Network analysis was then carried out to identify key gene (index gene) modules present in the model underlying the progression. Within this dataset, SIs were found to be very closely correlated with all the AD neuropathology biomarkers (R ~ 0.5, p < 1e-11) and global cognitive function (R = -0.68, p < 2.2e-16). We then applied the model to additional transcriptomic datasets from different brain regions (MAYO, n = 266; MSBB, n = 214), and observed that the model remained significantly predictive (p < 1e-3) of neuropathology and clinical severity. The index genes that significantly contributed to the model were integrated with AD co-expression regulatory networks, resolving two discrete gene modules that are implicated in vascular and metabolic dysfunction in different cell types respectively. Our work demonstrates the generalizability of this signature to frontal and temporal cortex measurements and additional brain donors with AD, other age-related neurological disorders and controls; and revealed the transcriptomic network modules contribute to neuropathological and clinical disease severity. This study illustrates the promise of using deep learning methods to analyze heterogeneous omics data and discover potentially targetable molecular networks that can inform the development, treatment and prevention of neurodegenerative diseases like AD.

scholarly journals The Association between the Usage of Non-Steroidal Anti-Inflammatory Drugs and Cognitive Status: Analysis of Longitudinal and Cross-Sectional Studies from the Global Alzheimer’s Association Interactive Network and Transcriptomic Data

2020 ◽  
Vol 10 (12) ◽  
pp. 961
Author(s):  
Robert Morris ◽  
Kyle Armbruster ◽  
Julianna Silva ◽  
Daniel James Widell ◽  
Feng Cheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Arachidonic Acid ◽  
Cognitive Status ◽  
Cross Sectional ◽  
Transcriptomic Data ◽  
Age Related ◽  
Interactive Network ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

The degenerative cognitive and physical decline of Alzheimer patients, coupled with the extensive psychological and economic tolls imposed on family members that serve as caretakers, necessitate the discovery of effective cures and preventative measures for age-related cognitive depreciation. In the journey of Alzheimer’s disease treatment discovery, several cross-sectional and longitudinal studies have delineated a noticeable association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs), a class of low-cost drugs with minimal side effects, and the alleviation of age-related memory impairment. In this study, four datasets (two cross-sectional and two longitudinal studies) derived from the Global Alzheimer’s Association Interactive Network (GAAIN) were analyzed. The significant association between the usage of NSAIDs and better cognitive status was observed. The results agree with the findings of previous studies that the use of NSAIDs may be beneficial in the early stages of Alzheimer’s disease. Transcriptomic data show that ibuprofen treatment results in upregulation of several genes involved in arachidonic acid metabolism including PPARγ, Cyp4a12b, Cyp2c66, and Cyp2c37 in the hippocampus. The increase in conversion of arachidonic acid into anti-inflammatory 16C and 18C dicarboxylic acids as well as epoxyeicosatrienoic acids may play a role in reducing the risk of Alzheimer’s disease development.

SPECIFIC PROPERTIES OF TUBULIN IN THE PREFRONTAL CORTEX IN CONTROL, SCHIZOPHRENIA AND VASCULAR DEMENTIA

2020 ◽  
pp. 65-71
Author(s):  
Burbaeva G.Sh. ◽  
Androsova L.V. ◽  
Vorobyeva E.A. ◽  
Savushkina O.K.
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Vascular Dementia ◽  
Binding Activity ◽  
Nephelometric Method ◽  
Rate Of Polymerization ◽  
Mental Diseases ◽  
And Control ◽  
The Brain

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

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