Abstract Alzheimer Research Articles

Drug information of Aducanumab and its effectiveness for Alzheimer’s disease: A clinical review

Alzheimer’s disease (AD) is the main cause of disability in people older than 60 years. More than 1 million cases per year reported in India. AD and other kinds of dementia are more common as individuals become older, affecting 1 in every 14 people over the age of 65 and 1 in every 6 people over the age of 80. ADUHELM (Aducanumab) is a monoclonal antibody, new class of medication needed for treatment of AD. The latest drug used to treat underlying cause of AD and recent studies shown to be efficacious and safe for the AD. Our review emphasizes on the drug information of Aducanumab and its clinical importance in AD.

Alzheimer’s disease and Aβ pathways

Alzheimer's disease (AD) is a neurodegenerative disease which is one of the major health issues globally. It is the 6th cause of death in the United States. Approximately, 60–70% of cases of dementia are caused by AD. The disease advances with age worsening the symptoms that include problems with declining memory, language, mood swings, loss of motivation, self-neglect, and other behavioral issues. AD patients need a long-term health care and hospital services as the disease worsens with the advancing of their age. However, proper medications and treatment is still unavailable as the cause of AD is poorly understood.

Tieguanyin Oolong Tea Extracts Alleviate Behavioral Abnormalities by Modulating Neuroinflammation in APP/PS1 Mouse Model of Alzheimer's Disease.

Alzheimer’s disease (AD) is a common neurodegenerative disease; tea components have important neuroprotective effects. This article explores the effects and mechanisms of Qingxiang Tiguanyin (Tgy-Q), Nongxiang Tieguanyin (Tgy-N), and Chenxiang Tieguanyin (Tgy-C) extracts on APP/PS1 AD model mice. Morris water maze and new object recognition experiments show that Tieguanyin extracts can effectively enhance the cognitive ability of APP/PS1 mice. H&E staining, Nissl staining, and immunohistochemical staining show that Tieguanyin extracts make nerve cell boundaries and nucleoli become clearer, relieve nucleus pyknosis, and effectively reduce Aβ1-40 and Aβ1-42 in the hippocampus and cortex. They also restore the morphology of microglia and astrocytes. In addition, Tieguanyin extracts can balance the oxidative stress level in the brain of APP/PS1 mice by improving the antioxidant capacity. Western blot results show that Tieguanyin extracts can reduce the expression of NF-κB p65, TNF-α, IL-1β, IL-6, COX-2, and iNOS in mouse brain, which demonstrates that Tieguanyin extracts improves cognitive ability by alleviating inflammation. This article demonstrates for the first time that Tieguanyin extracts can inhibit the excessive activation of the NF-κB p65 signaling pathway and improve the antioxidant capacity in the cerebral cortex and hippocampus, to improve the cognitive ability of APP/PS1 mice. Our results shed light into the beneficial of Tieguanyin tea extracts on preventing and alleviating AD diseases.

Effects of gut microbiota and probiotics on Alzheimer's disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high morbidity, disability, and fatality rate, significantly increasing the global burden of public health. The failure in drug discovery over the past decades has stressed the urgency and importance of seeking new perspectives. Recently, gut microbiome (GM), with the ability to communicate with the brain bidirectionally through the microbiome–gut–brain axis, has attracted much attention in AD-related studies, owing to their strong associations with amyloids, systematic and focal inflammation, impairment of vascular homeostasis and gut barrier, mitochondrial dysfunction, etc., making the regulation of GM, specifically supplementation of probiotics a promising candidate for AD treatment. This article aims to review the leading-edge knowledge concerning potential roles of GM in AD pathogenesis and of probiotics in its treatment and prevention.

Graph Theory-Based Brain Network Connectivity Analysis and Classification of Alzheimer’s Disease

Alzheimer’s Disease (AD) is basically a progressive neurodegenerative disorder associated with abnormal brain networks that affect millions of elderly people and degrades their quality of life. The abnormalities in brain networks are due to the disruption of White Matter (WM) fiber tracts that connect the brain regions. Diffusion-Weighted Imaging (DWI) captures the brain’s WM integrity. Here, the correlation betwixt the WM degeneration and also AD is investigated by utilizing graph theory as well as Machine Learning (ML) algorithms. By using the DW image obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, the brain graph of each subject is constructed. The features extracted from the brain graph form the basis to differentiate between Mild Cognitive Impairment (MCI), Control Normal (CN) and AD subjects. Performance evaluation is done using binary and multiclass classification algorithms and obtained an accuracy that outperforms the current top-notch DWI-based studies.

The Therapeutic Potential of Synthetic and Natural Cannabinoids in Treating Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most prevalent and debilitating neurodegenerative diseases in the world, highlighting the need for research on novel treatments and therapies. Previous studies have found that the body’s endocannabinoid system (ECS) interacts closely with its neural system, making it a potential avenue for the treatment of neurological disorders. One hallmark of AD is the accumulation of amyloid-beta (Aβ) in the brain and its potentially detrimental effects on cognitive function. Cannabis-based drugs have been observed to regulate Aβ modifications and inhibit AD progression. Furthermore, cannabinoids have been noted to reduce inflammation and neurotoxicity. Synthetic cannabinoids were able to rescue memory deficits and neurodegeneration, and reduce immunoreactivity. Similarly, natural cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) demonstrate therapeutic potential by interacting with the cholinergic system, and reversing the symptoms of AD. Although further research and testing are needed, it is evident that the use of cannabinoids shows promise for future treatment in AD patients.

Technological prospecting of music therapy in Alzheimer's disease

Alzheimer's disease (AD) is characterized by cognitive impairment and progressive memory loss and drug treatments have limited efficacy. Thus, non-pharmacological interventions, such as music therapy, have shown to be promising as supporting pharmacological treatment and, therefore, may arouse commercial interest regarding the development of this type of product. Thus, this study aims to carry out a patentometric survey on patent registrations with music therapy in the treatment of AD. A systematic search was carried out from 2000 to 2020 on the Orbti-Questel website, searching for documents referring to music therapies in AD. The terms “Alzheimer music methodology active therapy” and “Alzheimer music methodology passive therapy” were used. After searching, reading, and excluding duplicate results, we found four patent families referring to music therapy in AD and all were selected as a result, which was considered little compared to the number of studies published on the subject.

How can libraries support dementia friendly communities? The study into perceptions and experiences of Croatian public librarians

Alzheimer’s Disease (AD), the most common cause of dementia, is an incurable neurological disease with an unknown cause. Since AD is not only social and health challenge but also an economic and fiscal burden and its prevalence is expected to grow exponentially as world population gets older, in 2012 the World Health Organization (WHO) and Alzheimer’s Disease International (ADI) recognized dementia as a global public health priority. Although librarians have not generally been recognized as professionals caring for persons with dementia, recent research indicates that public libraries can contribute to the development of dementia friendly communities by supporting social inclusion, self-efficacy and capacity building of persons with AD, and by providing support to their informal caregivers (CGs). The research reported in this paper aims to examine the role of Croatian public libraries in building a dementia friendly communities, in a country where information, health and social care systems for D patients and their CGs are not sufficiently developed (Rušac, 2016; Petr Balog et al., 2020). With the help of quantitative (online survey) methodology authors explore how Croatian public libraries tailor their spaces, collections, programs and services in order to enhance the everyday experience of persons with AD and their CGs.

Difficulties in diagnosing atypical variants of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

Mitochondrial Dysfunction in Alzheimer’s Disease and Possible Therapeutic Targets to Prevent Progression of Alzheimer’s Disease

Alzheimer’s Disease (AD) is the most frequent cause of dementia in aged population. Till now, there is no effective treatment for AD. Now various studies have kinked AD to mitochondrial dysfunction, due to accumulation of Aβaggregates, neurofibrillary tangles, cholinergic transmission, oxidative stress and neuroinflammation causing neurodegeneration and cognitive decline seen in AD. Here in this article, how the mitochondrial dysfunction/dynamics are involved in the pathogenesis of cognitive decline seen in cases of AD and various therapeutics targeted against mitochondrial dysfunctions are described, thereby causing a ray of hope for preventing progression of AD.

Disturbance of phylogenetic layer-specific adaptation of human brain gene expression in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with typical neuropathological hallmarks, such as neuritic plaques and neurofibrillary tangles, preferentially found at layers III and V. The distribution of both hallmarks provides the basis for the staging of AD, following a hierarchical pattern throughout the cerebral cortex. To unravel the background of this layer-specific vulnerability, we evaluated differential gene expression of supragranular and infragranular layers and subcortical white matter in both healthy controls and AD patients. We identified AD-associated layer-specific differences involving protein-coding and non-coding sequences, most of those present in the subcortical white matter, thus indicating a critical role for long axons and oligodendrocytes in AD pathomechanism. In addition, GO analysis identified networks containing synaptic vesicle transport, vesicle exocytosis and regulation of neurotransmitter levels. Numerous AD-associated layer-specifically expressed genes were previously reported to undergo layer-specific switches in recent hominid brain evolution between layers V and III, i.e., those layers that are most vulnerable to AD pathology. Against the background of our previous finding of accelerated evolution of AD-specific gene expression, here we suggest a critical role in AD pathomechanism for this phylogenetic layer-specific adaptation of gene expression, which is most prominently seen in the white matter compartment.

Imbalances in Copper or Zinc Concentrations Trigger Further Trace Metal Dyshomeostasis in Amyloid-Beta Producing Caenorhabditis elegans.

Alzheimer's Disease (AD), a progressive neurodegenerative disease characterized by the buildup of amyloid-beta (Aβ) plaques, is believed to be a disease of trace metal dyshomeostasis. Amyloid-beta is known to bind with high affinity to trace metals copper and zinc. This binding is believed to cause a conformational change in Aβ, transforming Aβ into a configuration more amenable to forming aggregations. Currently, the impact of Aβ-trace metal binding on trace metal homeostasis and the role of trace metals copper and zinc as deleterious or beneficial in AD remain elusive. Given that Alzheimer's Disease is the sixth leading cause of adult death in the U.S., elucidating the molecular interactions that characterize Alzheimer's Disease pathogenesis will allow for better treatment options. To that end, the model organism C. elegans is used in this study. C. elegans, a transparent nematode whose connectome has been fully established, is an amenable model to study AD phenomena using a multi-layered, interconnected approach. Aβ-producing and non-Aβ-producing C. elegans were individually supplemented with copper and zinc. On day 6 and day 9 after synchronization, the percent of worms paralyzed, concentration of copper, and concentration of zinc were measured in both groups of worms. This study demonstrates that dyshomeostasis of trace metals copper or zinc triggers further trace metal dyshomeostasis in Aβ-producing worms, while dyshomeostasis of copper or zinc triggers a return to equilibrium in non-Aβ-producing worms. This supports the characterization of Alzheimer's Disease as a disease of trace metal dyshomeostasis.

Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer\u2019s disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to dementia and behavioral changes. Extracellular deposition of amyloid plaques (Aβ) and intracellular deposition of neurofibrillary tangles in neurons are the major pathogenicities of AD. However, drugs targeting these therapeutic targets are not effective. Therefore, novel targets for the treatment of AD urgently need to be identified. Expression of the mesoderm-specific transcript (Mest) is regulated by genomic imprinting, where only the paternal allele is active for transcription. We identified hypermethylation on the Mest promoter, which led to a reduction in Mest mRNA levels and activation of Wnt signaling in brain tissues of AD patients. Mest knockout (KO) using the CRIPSR/Cas9 system in mouse embryonic stem cells and P19 embryonic carcinoma cells leads to neuronal differentiation arrest. Depletion of Mest in primary hippocampal neurons via lentivirus expressing shMest or inducible KO system causes neurodegeneration. Notably, depletion of Mest in primary cortical neurons of rats leads to tau phosphorylation at the S199 and T231 sites. Overall, our data suggest that hypermethylation of the Mest promoter may cause or facilitate the progression of AD.

Classification of Alzheimer Condition using MR Brain Images and Inception-Residual Network Model

Abstract Alzheimer’s Disease (AD) is an irreversible progressive neurodegenerative disorder. Magnetic Resonance (MR) imaging based deep learning models with visualization capabilities are essential for the precise diagnosis of AD. In this study, an attempt has been made to categorize AD and Healthy Controls (HC) using structural MR images and an Inception-Residual Network (ResNet) model. For this, T1- weighted MR brain images are acquired from a public database. These images are pre-processed and are applied to a two-layer Inception-ResNet-A model. Additionally, Gradient weighted Class Activation Mapping (Grad-CAM) is employed to visualize the significant regions in MR images identified by the model for AD classification. The network performance is validated using standard evaluation metrics. Results demonstrate that the proposed Inception-ResNet model differentiates AD from HC using MR brain images. The model achieves an average recall and precision of 69%. The Grad- CAM visualization identified lateral ventricles in the mid-axial slice as the most discriminative brain regions for AD classification. Thus, the computer aided diagnosis study could be useful in the visualization and automated analysis of AD diagnosis with minimal medical expertise.

Neuroprotective effect of lacosamide on cognitive dysfunction in Streptozotocin induced Alzheimer disease

Abstract Alzheimer disease (AD) is a chronic and progressive neurodegenerative disorder characterized by memory loss and cognition impairment. A link has been established between AD and epilepsy sharing multiple mechanisms and pathogenesis. Similar Hippocampal changes have been found between both diseases. Choosing antiepileptic drug in AD patient represent a great a challenge especially with increase seizure risk in AD patients. Lacosamide, antiepileptic drug, was reported to have a neuroprotective effect in animal models and a histone deacetylase inhibition activity. This study was designed to investigate the potential effect of chronic lacosamide treatment in Streptozotocin induced AD in male Wistar rats. Methods AD animal model was induced with single bilateral intracerebroventricular injection of STZ (3 mg/kg) on day one. Lacosamide (30 mg/kg orally, once daily) was administrated for 21 days. Cognitive function assessment was done with Morris Water Maze (MWM) and Y Maze tasks. APP and MAPT mRNA level were measured. Results ICV-STZ caused significant prolongation in Escape latency time and reduction in time spent in target quadrant in MWM and reduction in spontaneous alteration ratio in Y Maze compared to control group. STZ induced Up-regulation in Amyloid precursor protein and Microtubule associated protein tau gene expression. Chronic Lacosamide treatment attenuated STZ induced cognitive impairment and mitigated APP and MAPT induced expression with STZ. Conclusion Lacosamide has a neuroprotective effect against STZ induced cognitive deficits ameliorating Aβ and Tau pathology.

Olfactory dysfunction in Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia. Olfactory dysfunction is detected at preclinical stage of this disease, this is important for the early appointment of therapy. The smell identifcation process involves the olfactory and orbitofrontal cortex, mediobasal structures of the temporal region, including the entorhinal cortex and hippocampus, which makes it extremely sensitive to neurodegeneration, especially of the Alzheimer's type. In patients at risk of developing AD (for example, carriers of the APOE4 genotype), patients with mild cognitive impairment and subjective cognitive decline also have olfactory dysfunction, which increases with the progression of cognitive defcit. This article presents the proposed mechanisms of hyposmia development in patients with Alzheimer's disease, the main methods of its study, such as olfactory tests, evoked olfactory potential, MRI and functional MRI, as well as data from population studies of recent years.

Neuroprotective Effect of Danggui Shaoyao San via the Mitophagy-Apoptosis Pathway in a Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a serious neurodegenerative disease. While the main pathological characteristic of AD is widely believed to be the accumulation of amyloid-beta (Aβ) in neurons around neurofibrillary plaques, the molecular mechanism of pathological changes is not clear. Traditional Chinese medicine offers many treatments for AD. Among these, Danggui Shaoyao San (DSS) is a classic prescription. In this study, an AD model was established by injecting Aβ 1–42 into the brains of rats, which were then treated with different concentrations of Danggui Shaoyao San (sham operation; model; and Danggui Shaoyao San high-dose, medium-dose, and low-dose intervention groups). The Morris water maze test was used to assess the learning and memory abilities of the animals in each group. Nissl staining was used to detect neurons. Mitophagy was evaluated by transmission electron microscopy and immunofluorescence colocalization. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression levels of autophagy- and apoptosis-related proteins were measured by western blot. Compared to the model group, the groups of AD rats administered medium and high doses of Danggui Shaoyao San showed significantly increased learning and memory abilities (P < 0.05), as well as significantly increased autophagosomes in the hippocampus. Moreover, the expression of PTEN-induced kinase 1 (PINK1), Parkin, and microtubule-associated protein light chain 3 (LC3-I/LC3-II) was increased, while that of p62 was significantly decreased (P < 0.05). The neuronal apoptosis rate was also significantly decreased, the Bcl-2/Bax ratio was significantly increased, and the cleaved caspase-3 protein expression was significantly decreased (P < 0.05). Therefore, Danggui Shaoyao San inhibited neuronal apoptosis in AD rats via a mechanism that may be related to the activation of the PINK1-Parkin-mediated mitophagy signaling pathway.

Potential Roles of Sestrin2 in Alzheimer's Disease: Antioxidation, Autophagy Promotion, and Beyond.

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

An efficient context-aware screening system for Alzheimer's disease based on neuropsychology test

Alzheimer's disease (AD) and other dementias have become the fifth leading cause of death worldwide. Accurate early detection of the disease and its precursor, Mild Cognitive Impairment (MCI), is crucial to alleviate the burden on the healthcare system. While most of the existing work in the literature applied neural networks directly together with several data pre-processing techniques, we proposed in this paper a screening system that is to perform classification based on automatic processing of the transcripts of speeches from the subjects undertaking a neuropsychological test. Our system is also shown applicable to different datasets and languages, suggesting that our system holds a high potential to be deployed widely in hospitals across regions. We conducted comprehensive experiments on two different languages datasets, the Pitt dataset and the NTUHV dataset, to validate our study. The results showed that our proposed system significantly outperformed the previous works on both datasets, with the score of the area under the receiver operating characteristic curve (AUROC) of classifying AD and healthy control (HC) being as high as 0.92 on the Pitt dataset and 0.97 on the NTUHV dataset. The performance on classifying MCI and HC remained promising, with the AUROC being 0.83 on the Pitt dataset and 0.88 on the NTUHV dataset.

MiR-485-5p alleviates Alzheimer's disease progression by targeting PACS1.

Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.