Increased astrocyte representation in the hippocampus of 5xFAD mice

Introduction: Alzheimer's disease is the most common neurodegenerative disorder, characterized by the formation of amyloid plaques and the neurofibrillary tangles in the brain of an ill person, leading to neuronal damage and loss. Activation of astrocytes and astrogliosis occurs along with this process. Due to ethical limitations in working with human tissue, numerous transgenic animal models have been developed to study the pathogenesis of these processes. Early Ab deposition is observed in the cortex and the hippocampus. Aim: This study aimed to determine the difference in the presence of GFAP positive cells in the hippocampus between transgenic 5xFAD mice aged 36 weeks and their corresponding controls. Material and Methods: The 5xFAD mice model of Alzheimer's disease was used, characterized by early formation of amyloid plaques but without the presence of neurofibrillar tangles. Transgenic and control animals were sacrificed at 36 weeks of age. The visualization of GFAP-positive cells in the hippocampus of their brains was done by using immunohistochemistry and antibody for glial fibrillary acidic protein - GFAP, the major marker of astrocytes. Quantification of immuno-reactivity was done by using the Icy software system. Results: There was a statistically significant difference in the expression of GFAP in the dentate gyrus and the granular zone of the hippocampus between the transgenic and control group at 36 weeks of age, while the significant change in the CA1-3 regions was not observed between investigated groups. Conclusion: Obtained results confirm the involvement of astrogliosis in the pathophysiology of Alzheimer's disease and indicate an earlier occurrence of astrogliosis in the dentate gyrus and granular zone, in relation to other regions of the hippocampus, in the 36-week-old 5xFAD mice.

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Investigation of five polymorphic DNA markers associated with late onset Alzheimer disease

Genetika ◽

10.2298/gensr1302503g ◽

2013 ◽

Vol 45 (2) ◽

pp. 503-514 ◽

Cited By ~ 7

Author(s):

Jalal Gharesouran ◽

Maryam Rezazadeh ◽

Mohaddes Mojtaba

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dna Markers ◽

Neurodegenerative Disorder ◽

Late Onset ◽

The Elderly ◽

Healthy Controls ◽

Genotype Frequencies ◽

Significant Difference ◽

And Control

Alzheimer's disease is a complex neurodegenerative disorder characterized by memory and cognitive impairment and is the leading cause of dementia in the elderly. The aim of our study was to examine the polymorphic DNA markers CCR2 (+190 G/A), CCR5?32, TNF-? (-308 G/A), TNF-? (-863 C/A) and CALHM1 (+394 C/T) to determine the relationship between these polymorphisms and the risk of late onset Alzheimer's disease in the population of Eastern Azerbaijan of Iran. A total of 160 patient samples and 163 healthy controls were genotyped by PCR-RFLP and the results confirmed using bidirectional sequencing. Statistical analysis of obtained data revealed non-significant difference between frequency of CCR5?32 in case and control groups. The same result was observed for TNF-? (-863 C/A) genotype and allele frequencies. Contrary to above results, significant differences were detected in frequency of TNF-? (-308 G/A) and CCR2-64I genotypes between the cases and healthy controls. A weak significant difference observed between allele and genotype frequencies of rs2986017 in CALHM1 (+394 C/T; P86L) in patient and control samples. It can be concluded that the T allele of P86L variant in CALHM1 & +190 G/A allele of CCR2 have a protective role against abnormal clinical features of Alzheimer's disease.

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Alexithymia in Alzheimer’s Disease

Journal of Clinical Medicine ◽

10.3390/jcm10010044 ◽

2020 ◽

Vol 10 (1) ◽

pp. 44

Author(s):

Eva Mª Arroyo-Anlló ◽

Corinne Souchaud ◽

Pierre Ingrand ◽

Jorge Chamorro Sánchez ◽

Alejandra Melero Ventola ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Abilities ◽

Rating Scale ◽

Mood State ◽

Neuropsychological Test ◽

Control Group ◽

Control Groups ◽

Significant Difference ◽

And Control

Alexithymia is widely recognized as the inability to identify and express emotions. It is a construct which consists of four cognitive traits such as difficulty in identifying feelings, describing feelings to others, externally oriented thinking, and limited imaginative capacity. Several studies have linked alexithymia to cognitive functioning, observing greater alexithymia scores associated with poorer cognitive abilities. Despite Alzheimer’s disease (AD) being a neurodegenerative pathology characterized by cognitive troubles from the early stages, associated to behavioral and emotional disturbances, very few investigations have studied the alexithymia in AD. These studies have shown that alexithymia scores—assessed with Toronto Alexithymia Scale (TAS)—were greater in AD patients than healthy participants. The objective of the study was to investigate if the alexithymia was present in patients with mild AD. We hypothesized that the AD group would show more alexithymia features than the control group. We evaluated 54 subjects, including 27 patients diagnosed with mild AD and 27 normal healthy controls, using the Shalling Sifneos Psychosomatic Scale (SSPS-R) and a neuropsychological test battery. Using non-parametric statistical analyses—Wilcoxon and Mann–Whitney U tests—we observed that the SSPS-R scores were similar in the AD and control groups. All participants showed SSPS-R scores below to 10 points, which means no-alexithymia. We did not find significant correlations between SSPS-R scores and cognitive variables in both groups (p > 0.22), but we observed a negative association between name abilities and alexithymia, but it does not reach to significance (p = 0.07). However, a significant correlation between SSPS-R score and mood state, assessed using Zerssen Rating Scale, was found in both groups (p = 0.01). Because we did not find a significant difference in the alexithymia assessment between both subject groups, pot hoc analyses were computed for each item of the SSPS-R. We made comparisons of alexithymic responses percentages in each SSPS-R item between AD and control groups, using Fisher’s test. We observed that AD patients produced more alexithymic responses in some items of SSPS-R test than the control group, particularly about difficulties to find the words to describe feelings, as well as difficulties of imagination capacity and externally oriented thinking. The present results do not confirm our hypothesis and they do not support the results of previous studies revealing great alexithymia in AD.

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In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-021-91899-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eugene Kim ◽

Davide Di Censo ◽

Mattia Baraldo ◽

Camilla Simmons ◽

Ilaria Rosa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Plaques ◽

Transgenic Animals ◽

Surrounding Tissue ◽

Rodent Models ◽

Enhanced Mri ◽

5Xfad Mice ◽

Manganese Enhanced Mri

AbstractAmyloid plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Animals were given subcutaneous injections of MnCl2 and imaged in vivo using a 9.4 T Bruker scanner. MnCl2 improved signal-to-noise ratio but was not necessary to detect plaques in high-resolution images. Plaques were visible in all transgenic animals and no wild-types, and quantitative susceptibility mapping showed that they were more paramagnetic than the surrounding tissue. This, combined with beta-amyloid and iron staining, indicate that plaque MR visibility in both animal models was driven by plaque size and iron load. Longitudinal relaxation rate mapping revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. This was limited to the rhinencephalon in the TgF344-AD rats, while it was most significantly increased in the cortex of the 5xFAD mice. Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats. Multi-parametric MEMRI is a simple, viable method for detecting amyloid plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present the first in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.

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Lipid Peroxidation in Chronic Cerebral HypoperfusionInduced Neurodegeneration in Rats

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v10i2.560 ◽

2020 ◽

Vol 10 (2) ◽

Author(s):

Anil Kumar S ◽

Saif SA ◽

Oothuman P ◽

Mustafa MIA

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Lipid Peroxidation ◽

Neurodegenerative Disorders ◽

Neuronal Damage ◽

Neuronal Cell ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Control Group ◽

Vessel Occlusion

Introduction: Reduced cerebral blood ﬂ ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body ﬂ uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), ﬁnal product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signiﬁ cant (p<0.001) increase in the mean MDA concentration (12.296 ± 1.113 μM) in 2VO rats as compared to the control group (5.286 ± 0.363 μM) rats. Conclusion: Therapeutic strategies to modulate lipid peroxidation early throughout the course of the disease may be promising in slowing or possibly preventing neurodegenerative disorders.

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Rectifying Attenuated Store-Operated Calcium Entry as a Therapeutic Approach for Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205018666210119150613 ◽

2021 ◽

Vol 17 (12) ◽

pp. 1072-1087

Author(s):

Alexis S. Huang ◽

Benjamin C.K. Tong ◽

Aston J. Wu ◽

Xiaotong Chen ◽

Sravan G. Sreenivasmurthy ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Synaptic Plasticity ◽

Neurodegenerative Disorder ◽

Amyloid Plaques ◽

Store Depletion ◽

Store Operated Calcium Entry ◽

Cellular Signal ◽

Neuronal Functions ◽

Entry Mechanism

: Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Although the pathological hallmarks of AD have been identified, the derived therapies cannot effectively slow down or stop disease progression; hence, it is likely that other pathogenic mechanisms are involved in AD pathogenesis. Intracellular calcium (Ca2+) dyshomeostasis has been consistently observed in AD patients and numerous AD models and may emerge prior to the development of amyloid plaques and neurofibrillary tangles. Thus, intracellular Ca2+ disruptions are believed to play an important role in AD development and could serve as promising therapeutic intervention targets. : One of the disrupted intracellular Ca2+ signaling pathways manifested in AD is attenuated storeoperated Ca2+ entry (SOCE). SOCE is an extracellular Ca2+ entry mechanism mainly triggered by intracellular Ca2+ store depletion. Maintaining normal SOCE function not only provides a means for the cell to replenish ER Ca2+ stores but also serves as a cellular signal that maintains normal neuronal functions, including excitability, neurogenesis, neurotransmission, synaptic plasticity, and gene expression. However, normal SOCE function is diminished in AD, resulting in disrupted neuronal spine stability and synaptic plasticity and the promotion of amyloidogenesis. Mounting evidence suggests that rectifying diminished SOCE in neurons may intervene with the progression of AD. In this review, the mechanisms of SOCE disruption and the associated pathogenic impacts on AD will be discussed. We will also highlight the potential therapeutic targets or approaches that may help ameliorate SOCE deficits for AD treatment.

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Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319266 ◽

2019 ◽

Vol 90 (7) ◽

pp. 740-746 ◽

Cited By ~ 7

Author(s):

Martha S Foiani ◽

Claudia Cicognola ◽

Natalia Ermann ◽

Ione O C Woollacott ◽

Carolin Heller ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Frontotemporal Dementia ◽

Neurodegenerative Disorder ◽

The Novel ◽

Tau Pathology ◽

Total Tau ◽

Significant Difference ◽

T Tau

BackgroundFrontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer’s disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD.Methods86 participants were included: 66 with a clinical diagnosis within the FTD spectrum and 20 healthy controls. Immunoassays targeting tau fragments N-123, N-mid-region, N-224 and X-368, as well as a non-phosphorylated form of tau were measured in CSF, along with total-tau (T-tau) and phospho-tau (P-tau(181)). Patients with FTD were grouped based on their Aβ42 level into those likely to have underlying Alzheimer’s disease (AD) pathology (n=21) and those with likely frontotemporal lobar degeneration (FTLD) pathology (n=45). The FTLD group was then subgrouped based on their underlying clinical and genetic diagnoses into those with likely tau (n=7) or TDP-43 (n=18) pathology.ResultsSignificantly higher concentrations of tau N-mid-region, tau N-224 and non-phosphorylated tau were seen in both the AD group and FTLD group compared with controls. However, none of the novel tau species showed a significant difference between the AD and FTLD groups, nor between the TDP-43 and tau pathology groups. In a subanalysis, normalising for total-tau, none of the novel tau species provided a higher sensitivity and specificity to distinguish between tau and TDP-43 pathology than P-tau(181)/T-tau, which itself only had a sensitivity of 61.1% and specificity of 85.7% with a cut-off of <0.109.ConclusionsDespite investigating multiple novel CSF tau fragments, none show promise as an FTD biomarker and so the quest for in vivo markers of FTLD-tau pathology continues.

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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

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17103398 ◽

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.

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Altered Theta Oscillations and Aberrant Cortical Excitatory Activity in the 5XFAD Model of Alzheimer’s Disease

Neural Plasticity ◽

10.1155/2015/781731 ◽

2015 ◽

Vol 2015 ◽

pp. 1-17 ◽

Cited By ~ 23

Author(s):

Magdalena Elisabeth Siwek ◽

Ralf Müller ◽

Christina Henseler ◽

Astrid Trog ◽

Andreas Lundt ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Cortical Excitability ◽

Theta Oscillations ◽

Dark Phase ◽

Model Of Alzheimer’S Disease ◽

Cortical Hyperexcitability ◽

5Xfad Mice ◽

Hippocampal Theta

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling.

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The Application Value of ApoE Gene Polymorphism in Alzheimer's Disease

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2148 ◽

2019 ◽

Vol 9 (10) ◽

pp. 1403-1407

Author(s):

Cong Chen ◽

Yuhui Zhang ◽

Bin Chen ◽

Chaosheng Zeng ◽

Min Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gene Polymorphism ◽

Apoe Genotype ◽

Apoe Gene ◽

Control Group ◽

Apolipoprotein E Polymorphism ◽

Abnormal Lipid Metabolism ◽

And Control ◽

Apoe Gene Polymorphism

To explore the association of apolipoprotein E polymorphism with Alzheimer's disease (AD), so as to provide possible research value for potential targeted therapy. 120 AD patients and 50 healthy volunteers were enrolled to extract fasting blood samples. ApoE gene polymorphism and blood lipids were tested in blood. ApoE gene and genotype frequency between AD group and control group were compared by PCR and sequencing methods. MMSE, CDR, and BPSD were used to determine the intelligence. ApoE genotype was detected by DNA microarray. ɛ4 carrier accounted for 45% in AD group, which was significantly elevated compared with control group (12%) (P < 0.05). TG, TC, and LDL-C levels were increased, while HDL-C was reduced in ɛ4 allele carriers (allP < 0.05). The MMSE scores of ApoEɛ4 genotype carriers in AD group were markedly lower than those of nonApoEɛ4 genotype carriers (P < 0.05) and control (P < 0.01). The proportion of dementia in ApoEɛ4 genotype carriers from AD group was apparently higher than the ɛ4 gene non-carriers (P < 0.05). The ApoEɛ4 gene is an AD risk factor. The changes of genotype and frequency of ApoEɛ4 gene are the main factors leading to abnormal lipid metabolism in AD patients, suggesting that ApoEɛ4 gene detection might be helpful for the early diagnosis and treatment of AD.

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The Potential Benefits of Nanotechnology in Treating Alzheimer’s Disease

BioMed Research International ◽

10.1155/2021/5550938 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Tan Sook Ling ◽

Shanthini Chandrasegaran ◽

Low Zhi Xuan ◽

Tong Li Suan ◽

Elaine Elaine ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Amyloid Plaques ◽

Disease Diagnosis ◽

Drug Bioavailability ◽

Potential Toxicity ◽

Alternative Approach ◽

Potential Benefits ◽

The Brain

Alzheimer’s disease is a neurodegenerative disorder that is caused by the accumulation of beta-amyloid plaques in the brain. Currently, there is no definitive cure available to treat Alzheimer’s disease. The available medication in the market has the ability to only slow down its progression. However, nanotechnology has shown its superiority that can be applied for medical usage and it has a great potential in the therapy of Alzheimer’s disease, specifically in the disease diagnosis and providing an alternative approach to treat Alzheimer’s disease. This is done by increasing the efficiency of drug delivery by penetrating and overcoming the blood-brain barrier. Having said that, there are limitations that need to be further investigated and researched in order to minimize the adverse effects and potential toxicity and to improve drug bioavailability. The recent advances in the treatment of Alzheimer’s disease using nanotechnology include the regeneration of stem cells, nanomedicine, and neuroprotection. In this review, we will discuss the advancement of nanotechnology which helps in the diagnosis and treatment of neurodegenerative disorders such as Alzheimer’s disease as well as its challenges.

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