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Current Alzheimer Research 2016Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive... (Review)
Review
Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive neuron-oriented research, an increasing body of evidence suggests that glial cells, namely astrocytes, microglia, NG2 glia and oligodendrocytes, may play an important role in the pathogenesis of this disease. In the first part of this review, AD pathophysiology in humans is briefly described and compared with disease progression in routinely used animal models. The relevance of findings obtained in animal models of AD is also discussed with respect to AD pathology in humans. Further, this review summarizes recent findings regarding the role/participation of glial cells in pathogenesis of AD, focusing on changes in their morphology, functions, proteins and gene expression profiles. As for astrocytes and microglia, they are fundamental for the progression and outcome of AD either because they function as effector cells releasing cytokines that play a role in neuroprotection, or because they fail to fulfill their homeostatic functions, ultimately leaving neurons to face excitotoxicity and oxidative stress. Next, we turn our attention towards NG2 glia, a novel and distinct class of glial cells in the central nervous system (CNS), whose role in a variety of human CNS diseases has begun to emerge, and we also consider the participation of oligodendrocytes in the pathogenesis and progression of AD. Since AD is currently an incurable disease, in the last part of our review we hypothesize about possible glia-oriented treatments and provide a perspective of possible future advancements in this field.
Topics: Alzheimer Disease; Animals; Humans; Neuroglia
PubMed: 26825092
DOI: 10.2174/1567205013666160129095924 -
Alzheimer's & Dementia : the Journal of... Sep 2011Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these...
Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer's Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer's disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.
Topics: Aged; Aggression; Alzheimer Disease; Apathy; Cognitive Dysfunction; Depressive Disorder; Humans; Neurocognitive Disorders
PubMed: 21889116
DOI: 10.1016/j.jalz.2011.05.2410 -
Current Aging Science Aug 2022There is considerable empirical evidence that unequivocally points to loneliness as a modifiable risk factor for the development of Alzheimer's disease and other related... (Review)
Review
There is considerable empirical evidence that unequivocally points to loneliness as a modifiable risk factor for the development of Alzheimer's disease and other related dementias. With the emergence of the COVID-19 pandemic and the resulting lockdown and social distancing, there has been a renewed interest in studying this topic. The present review examines the links between loneliness and Alzheimer's disease, with particular emphasis on the mechanisms common to both conditions.
Topics: Alzheimer Disease; COVID-19; Communicable Disease Control; Humans; Loneliness; Pandemics; Risk Factors
PubMed: 35249519
DOI: 10.2174/1874609815666220304195049 -
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 -
Journal of Alzheimer's Disease : JAD 2019Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed,... (Review)
Review
Population-based clinic-pathological studies have established that the most common pathological substrate of dementia in community-dwelling elderly people is mixed, especially Alzheimer's disease (AD) and cerebrovascular ischemic disease (CVID), rather than pure AD. While these could be just two frequent unrelated comorbidities in the elderly, epidemiological research has reinforced the idea that mid-life (age <65 years) vascular risk factors increase the risk of late-onset (age ≥ 65 years) dementia, and specifically AD. By contrast, healthy lifestyle choices such as leisure activities, physical exercise, and Mediterranean diet are considered protective against AD. Remarkably, several large population-based longitudinal epidemiological studies have recently indicated that the incidence and prevalence of dementia might be decreasing in Western countries. Although it remains unclear whether these positive trends are attributable to neuropathologically definite AD versus CVID, based on these epidemiological data it has been estimated that a sizable proportion of AD cases could be preventable. In this review, we discuss the current evidence about modifiable risk factors for AD derived from epidemiological, preclinical, and interventional studies, and analyze the opportunities for therapeutic and preventative interventions.
Topics: Alzheimer Disease; Genetic Predisposition to Disease; Humans; Prevalence; Risk Factors
PubMed: 30776012
DOI: 10.3233/JAD181028 -
Journal of Alzheimer's Disease : JAD 2017Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the... (Review)
Review
Alzheimer's disease (AD) is a neurodegenerative disorder that nowadays affects more than 40 million people worldwide and it is predicted to exponentially increase in the coming decades. Because no curative treatment exists, research on the pathophysiology of the disease, as well as the testing of new drugs, are mandatory. For these purposes, animal models constitute a valuable, although perfectible tool. This review takes a tour through several aspects of mouse models of AD, such as the generation of transgenic models, the relevance of the promoter driving the expression of the transgenes, and the concrete transgenes used to simulate AD pathophysiology. Then, transgenic mouse lines harboring mutated human genes at several loci such as APP, PSEN1, APOEɛ4, and ob (leptin) are reviewed. Therefore, not only the accumulation of the Aβ peptide is emulated but also cholesterol and insulin metabolism. Further novel information about the disease will allow for the development of more accurate animal models, which in turn will undoubtedly be helpful for bringing preclinical research closer to clinical trials in humans.
Topics: Alzheimer Disease; Animals; Disease Models, Animal; Humans; Mice, Transgenic
PubMed: 28304309
DOI: 10.3233/JAD-170045 -
Turk Psikiyatri Dergisi = Turkish... 2019Alzheimer's Disease (AD) is a neurodegenerative condition characterized by functional and structural changes in the brain that are increasingly better visualized with... (Review)
Review
OBJECTIVE
Alzheimer's Disease (AD) is a neurodegenerative condition characterized by functional and structural changes in the brain that are increasingly better visualized with the advances in new brain imaging techniques. Connectivity changes under the resting state condition especially in the internal connectivity network, named as the default mode network (DMN), are observed in AD. This paper aimed to investigate and discuss the findings on DMN connectivity.
METHOD
The studies carried out by functional magnetic resonance imaging (fMRI), using the two most widely applied techniques, the seed-based method and independent component analysis (ICA), have been investigated.
RESULTS
Studies generally indicate a progressive impairment in DMN connectivity during the course of AD. It has been also stated that DMN subsystems show differential connectivity patterns in the preclinical and prodromal stages of AD. There is also evidence suggesting that impairment in DMN connectivity could be associated with different connectivity patterns in other networks. Furthermore, findings point towards a relationship between DMN and AD-related neuropathology and genetic risk factors.
CONCLUSION
It may be proposed that AD is a generalized disconnection syndrome that causes functional impairments in resting state networks, particularly in DMN. In addition to this, AD-related functional connectivity changes observed in preclinical cases and risk carriers might be a potential bio-marker for AD.
Topics: Alzheimer Disease; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging
PubMed: 32594490
DOI: No ID Found -
Journal of Alzheimer's Disease : JAD 2014Currently, there is a pressing need to shift the focus to accurate detection of the earliest phase of increasingly preclinical Alzheimer's disease (AD). Meanwhile, the... (Review)
Review
Currently, there is a pressing need to shift the focus to accurate detection of the earliest phase of increasingly preclinical Alzheimer's disease (AD). Meanwhile, the growing recognition that the pathophysiological process of AD begins many years prior to clinically obvious symptoms and the concept of a presymptomatic or preclinical stage of AD are becoming more widely accepted. Advances in clinical identification of new measurements will be critical not only in the discovery of sensitive, specific, and reliable biomarkers of preclinical AD but also in the development of tests that will aid in the early detection and differential diagnosis of dementia and in monitoring disease progression. The goal of this review is to provide an overview of biomarkers for preclinical AD, with emphasis on neuroimaging and neurochemical biomarkers. We conclude with a discussion of emergent directions for AD biomarker research.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Early Diagnosis; Humans; Prodromal Symptoms
PubMed: 25024325
DOI: 10.3233/JAD-140843 -
Alzheimer's & Dementia : the Journal of... Jun 2016Several attempts have been made to treat Alzheimer's disease (AD) using anti-amyloid strategies with disappointing results. It is clear that the "amyloid cascade... (Review)
Review
Several attempts have been made to treat Alzheimer's disease (AD) using anti-amyloid strategies with disappointing results. It is clear that the "amyloid cascade hypothesis" alone cannot fully explain the neuronal damage in AD, as evidenced both by autopsy and imaging studies. Neuroinflammation plays a significant role in neurodegenerative diseases, whereas the debate is ongoing about its precise role, whether it is protective or harmful. In this review, we focus on the potential mechanism of glial activation and how local and systemic factors influence disease progression. We focus on neuroinflammation in AD, especially in the earliest stages, a vicious cycle of glial priming, release of pro-inflammatory factors, and neuronal damage. We review the evidence from imaging studies, regarding the temporal relationship between amyloid deposition and neuroinflammation, the influence of systemic inflammation on glial activation, both in acute and chronic stimulation and the relevance of inflammation as a diagnostic and therapeutic target.
Topics: Alzheimer Disease; Cytokines; Encephalitis; Humans; Neuroimaging
PubMed: 27179961
DOI: 10.1016/j.jalz.2016.02.010 -
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