Displaying publications 1 - 20 of 206 in total

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  1. Ang PS, Yeo SL, Koran L
    Dementia (London), 2023 Apr;22(3):628-645.
    PMID: 36764831 DOI: 10.1177/14713012231155979
    INTRODUCTION: This study examines the underlying visual communication strategies found in existing images of dementia in the public domain. By delineating how experiences of dementia are visualized and their consequent social interpretations, we aim to inform and advocate for a dementia-inclusive visual communication, that is, visual depictions that cultivate and represent a dementia-inclusive society.

    METHODS: The visuals were analyzed by employing the Visual Discourses of Disability (ViDD) framework that juxtaposes the "perspectivizing-personizing" cline with the "enabling-disabling" continuum. The data studied comprise a total of 432 images sourced from three domains, namely (1) The Star, a Malaysian mainstream English newspaper (2012-2021); (2) Alzheimer's Disease Foundation Malaysia (ADFM) website (2019-2021); and (3) the Ministry of Health Malaysia (2019-2021) website. Findings from the visual analyses were corroborated by four representatives of ADFM in a group interview.

    RESULTS: There is a predominance of stigmatized images, constructing dementia as a loss and deficit, thus depicting individuals in distanced suffering. Generic representations of people through stock images, a unique focus on the hands, representations of brain degeneration through abstractions and missing puzzle pieces are also prevalent. Despite these, the interview data confirmed that the perspectivizing aspect may be necessary to educate the public on what dementia entails. While personizing images that depict personhood and actual persons living with dementia are ideal, the use of stock images may be necessary if there is a need to maintain confidentiality and observe sensitivities. Similarly, images with positive emotions are encouraged but disabling ones are equally important to reflect reality and inculcate empathy.

    CONCLUSION: When capturing, selecting and publishing images of dementia, organizations should deliberate on different visual elements which evoke empowerment, advocacy, handicapping and othering implications as outlined in the ViDD framework. Any decision should only be made after considering the purposes of publications and implications such images have on the intended audiences.

    Matched MeSH terms: Alzheimer Disease*
  2. Wen MM, El-Salamouni NS, El-Refaie WM, Hazzah HA, Ali MM, Tosi G, et al.
    J Control Release, 2017 01 10;245:95-107.
    PMID: 27889394 DOI: 10.1016/j.jconrel.2016.11.025
    Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.
    Matched MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/etiology
  3. Lee JY, Lim MCX, Koh RY, Tsen MT, Chye SM
    Metab Brain Dis, 2024 Jun;39(5):985-1004.
    PMID: 38842660 DOI: 10.1007/s11011-024-01368-x
    Neurodegeneration, known as the progressive loss of neurons in terms of their structure and function, is the principal pathophysiological change found in the majority of brain-related disorders. Ageing has been considered the most well-established risk factor in most common neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). There is currently no effective treatment or cure for these diseases; the approved therapeutic options to date are only for palliative care. Ageing and neurodegenerative diseases are closely intertwined; reversing the aspects of brain ageing could theoretically mitigate age-related neurodegeneration. Ever since the regenerative properties of young blood on aged tissues came to light, substantial efforts have been focused on identifying and characterizing the circulating factors in the young and old systemic milieu that may attenuate or accentuate brain ageing and neurodegeneration. Later studies discovered the superiority of old plasma dilution in tissue rejuvenation, which is achieved through a molecular reset of the systemic proteome. These findings supported the use of therapeutic blood exchange for the treatment of degenerative diseases in older individuals. The first objective of this article is to explore the rejuvenating properties of blood-based therapies in the ageing brains and their therapeutic effects on AD. Then, we also look into the clinical applications, various limitations, and challenges associated with blood-based therapies for AD patients.
    Matched MeSH terms: Alzheimer Disease/metabolism; Alzheimer Disease/therapy
  4. Zareei M, Islam AKMM, Baharun S, Vargas-Rosales C, Azpilicueta L, Mansoor N
    Sensors (Basel), 2017 Sep 16;17(9).
    PMID: 28926952 DOI: 10.3390/s17092136
    New wireless network paradigms will demand higher spectrum use and availability to cope with emerging data-hungry devices. Traditional static spectrum allocation policies cause spectrum scarcity, and new paradigms such as Cognitive Radio (CR) and new protocols and techniques need to be developed in order to have efficient spectrum usage. Medium Access Control (MAC) protocols are accountable for recognizing free spectrum, scheduling available resources and coordinating the coexistence of heterogeneous systems and users. This paper provides an ample review of the state-of-the-art MAC protocols, which mainly focuses on Cognitive Radio Ad Hoc Networks (CRAHN). First, a description of the cognitive radio fundamental functions is presented. Next, MAC protocols are divided into three groups, which are based on their channel access mechanism, namely time-slotted protocol, random access protocol and hybrid protocol. In each group, a detailed and comprehensive explanation of the latest MAC protocols is presented, as well as the pros and cons of each protocol. A discussion on future challenges for CRAHN MAC protocols is included with a comparison of the protocols from a functional perspective.
    Matched MeSH terms: Alzheimer Disease
  5. Ismail NA, Leong Abdullah MFI, Hami R, Ahmad Yusof H
    Growth Factors, 2021 01 11;38(3-4):210-225.
    PMID: 33427532 DOI: 10.1080/08977194.2020.1864347
    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is highly expressed in the brain. It influences neuronal survival, growth and acts as a control centre for neurotransmitters. It also plays a crucial role in learning and memory. Current evidence indicates that BDNF may be a possible neurotrophic factor that controls cognitive functions under normal and neuropathological conditions. Recent findings indicate a reduction in cognitive performance in individuals with Alzheimer's disease (AD). This relationship between cognitive performance and AD is important for investigating both the time they overlap and the pathophysiological mechanism in each case. Therefore, this study reviewed the existing knowledge about BDNF and cognitive performance in the AD population. The findings support the idea that this tropic factor may be a potential biomarker for evaluating the changes in cognitive performance in AD.
    Matched MeSH terms: Alzheimer Disease*
  6. Siddiqui A, Akhtar S, Shah Z, Othman I, Kumari Y
    Curr Neuropharmacol, 2021;19(6):885-895.
    PMID: 32972344 DOI: 10.2174/1570159X18666200924122732
    It is a known fact that inflammation affects several physiological processes, including the functioning of the central nervous system. Additionally, impairment of lipid mechanisms/pathways have been associated with a number of neurodegenerative disorders and Alzheimer's Disease (AD) is one of them. However, much attention has been given to the link between tau and beta- amyloid hypothesis in AD pathogenesis/prognosis. Increasing evidences suggest that biologically active lipid molecules could influence the pathophysiology of AD via a different mechanism of inflammation. This review intends to highlight the role of inflammatory responses in the context of AD with the emphasis on biochemical pathways of lipid metabolism enzyme, 5-lipoxygenase (5- LO).
    Matched MeSH terms: Alzheimer Disease*
  7. Mitra S, Muni M, Shawon NJ, Das R, Emran TB, Sharma R, et al.
    Oxid Med Cell Longev, 2022;2022:7252882.
    PMID: 36035218 DOI: 10.1155/2022/7252882
    Tacrine is a drug used in the treatment of Alzheimer's disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca2+ homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer's disease. The variety both in structural make-up and biological functions of these substances is the main appeal for researchers' interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer's disease, as well as other neurological disorders like Parkinson's disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.
    Matched MeSH terms: Alzheimer Disease*
  8. Chong FP, Ng KY, Koh RY, Chye SM
    Cell Mol Neurobiol, 2018 Jul;38(5):965-980.
    PMID: 29299792 DOI: 10.1007/s10571-017-0574-1
    Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive function deficits. There are two major pathological hallmarks that contribute to the pathogenesis of AD which are the presence of extracellular amyloid plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. Despite extensive research that has been done on Aβ in the last two decades, therapies targeting Aβ were not very fruitful at treating AD as the efficacy of Aβ therapies observed in animal models is not reflected in human clinical trials. Hence, tau-directed therapies have received tremendous attention as the potential treatments for AD. Tauopathies are closely correlated with dementia and immunotherapy has been effective at reducing tau pathology and improving cognitive deficits in animal models. Thus, in this review article, we discussed the pathological mechanism of tau proteins, the key factors contributing to tauopathies, and therapeutic approaches for tauopathies in AD based on the recent progress in tau-based research.
    Matched MeSH terms: Alzheimer Disease/complications*; Alzheimer Disease/metabolism*
  9. Ng PY, Chang IS, Koh RY, Chye SM
    Metab Brain Dis, 2020 10;35(7):1049-1066.
    PMID: 32632666 DOI: 10.1007/s11011-020-00591-6
    Alzheimer's disease (AD) has been a worldwide concern for many years now. This is due to the fact that AD is an irreversible and progressive neurodegenerative disease that affects quality of life. Failure of some Phase II/III clinical trials in AD targeting accumulation of β-amyloid in the brain has led to an increase in interest in studying alternative treatments against tubulin-associated unit (Tau) pathology. These alternative treatments include active and passive immunisation. Based on numerous studies, Tau is reported as a potential immunotherapeutic target for tauopathy-related diseases including AD. Accumulation and aggregation of hyperphosphorylated Tau as neuropil threads and neurofibrillary tangles (NFT) are pathological hallmarks of AD. Both active and passive immunisation targeting Tau protein have shown the capabilities to decrease or prevent Tau pathology and improve either motor or cognitive impairment in various animal models. In this review, we summarise recent advances in active and passive immunisation targeting pathological Tau protein, and will discuss with data obtained from both animal and human trials. Together, we give a brief overview about problems being encountered in these immunotherapies.
    Matched MeSH terms: Alzheimer Disease/drug therapy*; Alzheimer Disease/immunology
  10. Chee KY, Yee OK, Gaillard F, Velakoulis D, Mohd Zain NR, Yogendren L, et al.
    Aust N Z J Psychiatry, 2017 Dec;51(12):1252-1253.
    PMID: 28762277 DOI: 10.1177/0004867417722642
    Matched MeSH terms: Alzheimer Disease/genetics*; Alzheimer Disease/physiopathology*
  11. Alam F, Islam MA, Sasongko TH, Gan SH
    Curr Pharm Des, 2016;22(28):4430-42.
    PMID: 27229721 DOI: 10.2174/1381612822666160527160236
    Although type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are two independent diseases, evidences from epidemiological, pathophysiological and animal studies have indicated a close pathophysiological relationship between these diseases. Due to the pathophysiological similarity of T2DM and AD, which includes insulin resistance and deficiency, protein aggregation, oxidative stress, inflammation, autophagocytosis and advanced glycation end products; AD is often referred to as "type 3 diabetes". In addition to the targeted regimens usually used for treating T2DM and AD individually, currently, anti-diabetic drugs are successfully used to reduce the cognitive decline in AD patients. Therefore, if a common pathophysiology of T2DM and AD could be clearly determined, both diseases could be managed more efficiently, possibly by shared pharmacotherapy in addition to understanding the broader spectrum of preventive strategies. The aim of this review is to discuss the pathophysiological bridge between T2DM and AD to lay the foundation for the future treatment strategies in the management of both diseases.
    Matched MeSH terms: Alzheimer Disease/physiopathology*; Alzheimer Disease/therapy
  12. Mohamad Nasir NF, Zainuddin A, Shamsuddin S
    J Mol Neurosci, 2018 Feb;64(2):157-161.
    PMID: 29260452 DOI: 10.1007/s12031-017-1005-y
    Alzheimer's disease (AD) is a neurodegenerative disease that is imposing an increasing burden on society. Currently, AD is the leading cause of senile dementia worldwide. Despite the long existence of AD, there is lack of therapies for AD, suggesting that new and effective treatment strategy must be explored. At present, sirtuin pathway has attracted attention from the researchers due to its promising results in laboratory models of aging. In addition, our understanding in the roles of sirtuin 6 in AD has expanded. It has been identified to be involved in telomere maintenance, DNA repair, genome integrity, energy metabolism, and inflammation, which ultimately regulate life span. Recent findings also demonstrate that sirtuin 6 is lacking in AD patients, proposing that it can be a new potential therapeutic target in AD. Therefore, exploring on how sirtuin 6 is related in AD manifestation may accelerate the research of AD further and benefits future AD patients. Keeping that in mind, this review aims to highlight the possible roles of sirtuin 6 in AD manifestation.
    Matched MeSH terms: Alzheimer Disease/genetics; Alzheimer Disease/metabolism*
  13. Rahim F, Javed MT, Ullah H, Wadood A, Taha M, Ashraf M, et al.
    Bioorg Chem, 2015 Oct;62:106-16.
    PMID: 26318401 DOI: 10.1016/j.bioorg.2015.08.002
    A series of thirty (30) thiazole analogs were prepared, characterized by (1)H NMR, (13)C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59±0.01 and 389.25±1.75μM when compared with the standard eserine (IC50, 0.85±0.0001μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59±0.01, 1.77±0.01, 6.21±0.01, 7.56±0.01, 8.46±0.01, 14.81±0.32 and 16.54±0.21μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3±0.50, 35.3±0.64, 36.6±0.70, 44.81±0.81, 46.36±0.84, 48.2±0.06 and 48.72±0.91μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.
    Matched MeSH terms: Alzheimer Disease*
  14. Wu M, Li M, Yuan J, Liang S, Chen Z, Ye M, et al.
    Pharmacol Res, 2020 05;155:104693.
    PMID: 32057896 DOI: 10.1016/j.phrs.2020.104693
    Hormone therapy continues to be a favourable option in the management of menopausal symptomatology, but the associated risk-benefit ratios with respect to neurodegenerative diseases remain controversial. The study aim was to determine the relation between menopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in human subjects. A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in menopausal women were reported in 28 studies. Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer's disease (OR 1.08, 95 % CI 1.03-1.14, I2: 69 %). This relationship was more pronounced in patients receiving the combined estrogen-progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer's disease was also identified (Coef1 = 0.0477, p1<0.001; Coef2 = -0.0932, p2<0.001). Similarly, pooled analysis revealed a significant association between hormone therapy and all-cause dementia (OR 1.16, 95 % CI 1.02-1.31, I2: 19 %). Interestingly, no comparable relationship was uncovered between hormone therapy as a whole and Parkinson's disease (OR 1.14, 95 % CI 0.95-1.38, I2: 65 %); however, sub-group analysis revealed a significant relationship between the disease and progestogen (OR 3.41, 95 % CI 1.23-9.46) or combined estrogen-progestogen formulation use (OR 1.49, 95 % CI 1.34-1.65). Indeed, this association was also found to be driven by duration of exposure (Coef1 = 0.0626, p1 = 0.04). This study reveals a significant direct relationship between the use of certain hormonal therapies and Alzheimer's disease, all-cause dementia, and Parkinson's disease in menopausal women. However, the association appears to shift in direct after five years in the context of Alzheimer's disease, adding further weight to the critical window or timing hypothesis of neurodegeneration and neuroprotection.
    Matched MeSH terms: Alzheimer Disease/epidemiology*
  15. Hsu JH, Liu CC, Chen IW, Wu JY, Huang PY, Liu TH, et al.
    Front Public Health, 2023;11:1293710.
    PMID: 38026272 DOI: 10.3389/fpubh.2023.1293710
    BACKGROUND: Mild cognitive impairment (MCI) is an intermediate stage between normal ageing and dementia. The early identification of MCI is important for timely intervention. The visual cognitive assessment test (VCAT) is a brief language-neutral screening tool for detecting MCI/mild dementia. This meta-analysis evaluated the diagnostic efficacy of the VCAT for MCI/mild dementia.

    METHODS: Medline, Embase, Google Scholar, and Cochrane Library were searched from their inception until August 2023 to identify studies using VCAT to diagnose MCI/mild dementia. The primary outcome was to assess the diagnostic accuracy of the VCAT for detecting MCI/mild dementia through area under the receiver operating characteristic curve (AU-ROC) analysis. The secondary outcome was to explore the correlation between VCAT scores and MCI/mild dementia presence by comparing scores among patients with and without MCI/mild dementia. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated.

    RESULTS: Five studies with 1,446 older adults (mean age 64-68.3 years) were included. The percentage of participants with MCI/mild dementia versus controls ranged from 16.5% to 87% across studies. All studies were conducted in Asian populations, mostly Chinese, in Singapore and Malaysia. The pooled sensitivity was 80% [95% confidence interval (CI) 68%-88%] and the specificity was 75% (95% CI 68%-80%). The AU-ROCC was 0.77 (95% CI 0.73-0.81). Patients with MCI/mild dementia had lower VCAT scores than the controls (mean difference -6.85 points, p 

    Matched MeSH terms: Alzheimer Disease*
  16. Srinivas P
    Med J Malaysia, 1999 Dec;54(4):541-9; quiz 550.
    PMID: 11072482
    Alzheimer's disease (AD) has become recognised as a major cause of morbidity and mortality in the ageing population worldwide. Over 20 million people worldwide are affected by AD, which ensures that the disease imposes a major economic burden. Alzheimer's disease is a progressive neurodegenerative disorder with characteristic clinical and neuropathological features. Neurofibrillary tangles, neuritic plaques and amyloid angiopathy occur in varying severity in brains of patient's with Alzheimer's disease. Biological markers of AD allowing an early definitive premorbid diagnoses are currently not available. Memory loss for recent events is invariable and often the earliest prominent symptom. Language disorders, difficulties with complex tasks, depression, psychotic symptoms and behavioral changes are other common manifestations of AD. Diagnosis involves the early detection of cognitive decline and ruling out other causes of dementia like vascular dementia, Lewy body dementia, fronto-temporal degeneration or reversible causes like hypothyroidism. Acetylcholinesterase inhibitors have shown to be effective in mild to moderate AD in improving the cognitive function of patients in clinical trials. Caregiver intervention programs have considerable potential to improve both the caregiver and patient quality of life.
    Matched MeSH terms: Alzheimer Disease/diagnosis*; Alzheimer Disease/psychology; Alzheimer Disease/therapy*
  17. Mah, S.L., George, P.
    Malaysian Family Physician, 2018;13(2):26-28.
    MyJurnal
    Dementia is typically characterized by the deterioration of cognitive abilities and is a common disorder
    among the elderly in Malaysia. However, behavioral and psychological symptoms are also present
    in approximately 90% of dementia patients.1 We report the manifestation of these symptoms in an
    elderly woman with dementia and the treatment thereof.
    Matched MeSH terms: Alzheimer Disease
  18. Se Thoe E, Fauzi A, Tang YQ, Chamyuang S, Chia AYY
    Life Sci, 2021 Jul 01;276:119129.
    PMID: 33515559 DOI: 10.1016/j.lfs.2021.119129
    Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which is mainly characterized by progressive impairment in cognition, emotion, language and memory in older population. Considering the impact of AD, formulations of pharmaceutical drugs and cholinesterase inhibitors have been widely propagated, receiving endorsement by FDA as a form of AD treatment. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis but merely targeting the symptoms so as to improve a patient's cognitive outcome. Hence, a search for better disease-modifying alternatives is put into motion. Having a clear understanding of the neuroprotective mechanisms and diverse properties undertaken by specific genes, antibodies and nanoparticles is central towards designing novel therapeutic agents. In this review, we provide a brief introduction on the background of Alzheimer's disease, the biology of blood-brain barrier, along with the potentials and drawbacks associated with current therapeutic treatment avenues pertaining to gene therapy, immunotherapy and nanotherapy for better diagnosis and management of Alzheimer's disease.
    Matched MeSH terms: Alzheimer Disease/genetics; Alzheimer Disease/immunology; Alzheimer Disease/therapy*
  19. Zakaria R, Wan Yaacob WM, Othman Z, Long I, Ahmad AH, Al-Rahbi B
    Physiol Res, 2017 09 22;66(4):553-565.
    PMID: 28406691
    Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats' response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD.
    Matched MeSH terms: Alzheimer Disease/chemically induced*; Alzheimer Disease/metabolism*; Alzheimer Disease/pathology
  20. Pahrudin Arrozi A, Shukri SNS, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Makpol S
    Appl Biochem Biotechnol, 2017 Nov;183(3):853-866.
    PMID: 28417423 DOI: 10.1007/s12010-017-2468-6
    Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations. Currently, most of the in vitro models used to study AD pathogenesis only examine the level of Aβ42 as a confirmation of successful model generation and only perform comparisons between wild-type APP and single mutants of the APP gene. Recent findings have shown that the Aβ42/40 ratio in cerebrospinal fluid (CSF) is a better diagnostic indicator for AD patients than is Aβ42 alone and that more extensive Aβ formation, such as accumulation of intraneuronal Aβ, Aβ plaques, soluble oligomeric Aβ (oAβ), and insoluble fibrillar Aβ (fAβ) occurs in TgCRND8 mice expressing a double-mutant form (Swedish and Indiana) of APP, later leading to greater progressive impairment of the brain. In this study, we generated SH-SY5Y cells stably transfected separately with wild-type APP, the Swedish mutation of APP, and the Swedish and Indiana mutations of APP and evaluated the APP expression as well as the Aβ42/40 ratio in those cells. The double-mutant form of APP (Swedish/Indiana) expressed markedly high levels of APP protein and showed a high Aβ2/40 ratio compared to wild-type and single-mutant cells.
    Matched MeSH terms: Alzheimer Disease/genetics; Alzheimer Disease/metabolism; Alzheimer Disease/pathology*
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