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Zoological Research Nov 2022Although great advances in elucidating the molecular basis and pathogenesis of Alzheimer's disease (AD) have been made and multifarious novel therapeutic approaches have... (Review)
Review
Although great advances in elucidating the molecular basis and pathogenesis of Alzheimer's disease (AD) have been made and multifarious novel therapeutic approaches have been developed, AD remains an incurable disease. Evidence shows that AD neuropathology occurs decades before clinical presentation. AD is divided into three stages: preclinical stage, mild cognitive impairment (MCI), and AD dementia. In the natural world, some animals, such as non-human primates (NHPs) and canines, can develop spontaneous AD-like dementia. However, most animals do not develop AD. With the development of transgenic techniques, both invertebrate and vertebrate animals have been employed to uncover the mechanisms of AD and study treatment methods. Most AD research focuses on early-onset familial AD (FAD) because FAD is associated with specific genetic mutations. However, there are no well-established late-onset sporadic AD (SAD) animal models because SAD is not directly linked to any genetic mutation, and multiple environmental factors are involved. Moreover, the widely used animal models are not able to sufficiently recapitulate the pathological events that occur in the MCI or preclinical stages. This review summarizes the common models used to study AD, from yeast to NHP models, and discusses the different applications, evaluation methods, and challenges related to AD animal models, as well as prospects for the evolution of future studies.
Topics: Animals; Dogs; Alzheimer Disease; Disease Models, Animal; Dog Diseases; Mutation
PubMed: 36317468
DOI: 10.24272/j.issn.2095-8137.2022.289 -
Tidsskrift For Den Norske Laegeforening... May 2021Alzheimer's disease is the most common cause of dementia globally. Its prevalence will increase considerably in the years to come, in pace with the increasing proportion...
Alzheimer's disease is the most common cause of dementia globally. Its prevalence will increase considerably in the years to come, in pace with the increasing proportion of older people. No disease-modifying treatment is currently available. Measures to mitigate risk in mid-life may potentially prevent or postpone up to 40 % of dementia cases at group level.
Topics: Aged; Alzheimer Disease; Humans
PubMed: 33950641
DOI: 10.4045/tidsskr.20.0919 -
The Journal of Prevention of... 2018Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD... (Review)
Review
Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Commonly characterized as ending in reproductive senescence, many symptoms of MT are neurological, including disruption of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, as well as depression and impairment in multiple cognitive domains. Preclinical studies have shown that, during MT, the estrogen network uncouples from the brain bioenergetic system. The resulting hypometabolic state could serve as the substrate for neurological dysfunction. Indeed, translational brain imaging studies demonstrate that 40-60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity and increased brain amyloid-beta deposition as compared to premenopausal women and to age-matched men. This review discusses the MT as a window of opportunity for therapeutic interventions to compensate for brain bioenergetic crisis and combat the subsequent increased risk for AD in women.
Topics: Alzheimer Disease; Brain; Female; Hormone Replacement Therapy; Humans; Menopause; Risk Factors
PubMed: 30298180
DOI: 10.14283/jpad.2018.34 -
Alzheimer's & Dementia : the Journal of... Sep 2018Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's... (Review)
Review
INTRODUCTION
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches.
METHODS
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.
RESULTS
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.
DISCUSSION
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
Topics: Alzheimer Disease; Animals; Gender Identity; Humans; Sex Characteristics
PubMed: 29907423
DOI: 10.1016/j.jalz.2018.04.008 -
Clinical Medicine (London, England) Jun 2016Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms... (Review)
Review
Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy.
Topics: Alzheimer Disease; Amyloid; Cholinesterase Inhibitors; Humans; Neuroprotective Agents
PubMed: 27251914
DOI: 10.7861/clinmedicine.16-3-247 -
Alzheimer's & Dementia : the Journal of... May 2011The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would...
Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.
The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious.
Topics: Alzheimer Disease; Biomarkers; Cognition Disorders; Humans; National Institute on Aging (U.S.); Practice Guidelines as Topic; United States
PubMed: 21514248
DOI: 10.1016/j.jalz.2011.03.003 -
Alzheimer's & Dementia : the Journal of... Mar 2016During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker... (Review)
Review
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
Topics: Alzheimer Disease; Animals; Brain; Disease Progression; Humans
PubMed: 27012484
DOI: 10.1016/j.jalz.2016.02.002 -
Dialogues in Clinical Neuroscience 2009More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's... (Review)
Review
More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's disease has had tremendous impact on the affected individuals, caregivers, and society. The etiological factors, other than older age and genetic susceptibility, remain to be determined. Nevertheless, increasing evidence strongly points to the potential risk roles of vascular risk factors and disorders (eg, cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions) and the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity) in the pathogenetic process and clinical manifestation of the dementing disorders. The long-term multidomain interventions toward the optimal control of multiple vascular risk factors and the maintenance of socially integrated lifestyles and mentally stimulating activities are expected to reduce the risk or postpone the clinical onset of dementia, including Alzheimer's disease.
Topics: Aging; Alzheimer Disease; Cardiovascular Diseases; Cognition; Humans; Incidence; Models, Biological; Prevalence; Risk Factors; Risk Reduction Behavior
PubMed: 19585947
DOI: 10.31887/DCNS.2009.11.2/cqiu -
International Journal of Molecular... Jan 2023There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer's disease (AD) across the globe.... (Review)
Review
There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer's disease (AD) across the globe. This paper examines the biochemical and clinical outlook and the social implications of the condition in relation to psychological aspects that may indicate a direction for further interventions. There is a scarcity of research on the effectiveness of using various psychological aspects of AD, a disease characterized by a process of transition from health and independence to a dependent state with a progressive loss of memory and functional skills. The paper investigates the biochemical and psychological aspects of AD and their significance for improving quality of life for patients with this disease. Psychological interventions based on, among other factors, biochemical studies, are conducted to improve the emotional wellbeing of AD patients and may assist in slowing down the progression of the disease. To date, however, no effective methods of AD treatment have been established.
Topics: Humans; Alzheimer Disease; Quality of Life
PubMed: 36674580
DOI: 10.3390/ijms24021059 -
Journal of Alzheimer's Disease : JAD 2017Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive... (Review)
Review
Excitatory glutamatergic neurotransmission via N-methyl-d-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. However, excessive NMDAR activity causes excitotoxicity and promotes cell death, underlying a potential mechanism of neurodegeneration occurred in Alzheimer's disease (AD). Studies indicate that the distinct outcomes of NMDAR-mediated responses are induced by regionalized receptor activities, followed by different downstream signaling pathways. The activation of synaptic NMDARs initiates plasticity and stimulates cell survival. In contrast, the activation of extrasynaptic NMDARs promotes cell death and thus contributes to the etiology of AD, which can be blocked by an AD drug, memantine, an NMDAR antagonist that selectively blocks the function of extrasynaptic NMDARs.
Topics: Alzheimer Disease; Humans; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate
PubMed: 27662322
DOI: 10.3233/JAD-160763