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Journal of Alzheimer's Disease : JAD 2018A growing body of evidence supports a clear association between Alzheimer's disease and diabetes and several mechanistic links have been revealed. This paper is mainly... (Review)
Review
A growing body of evidence supports a clear association between Alzheimer's disease and diabetes and several mechanistic links have been revealed. This paper is mainly devoted to the discussion of the role of diabetes-associated mitochondrial defects in the pathogenesis of Alzheimer's disease. The research experience and views of the author on this subject will be highlighted.
Topics: Alzheimer Disease; Animals; Diabetes Mellitus; Humans; Mitochondria
PubMed: 29562542
DOI: 10.3233/JAD-170931 -
Alzheimer's Research & Therapy Dec 2022Alpha-synuclein (α-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. α-Syn is an intrinsically disordered protein... (Review)
Review
BACKGROUND
Alpha-synuclein (α-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. α-Syn is an intrinsically disordered protein (IDP), and several types of structural conformations have been reported, depending on environmental factors. Since IDPs may have distinctive functions depending on their structures, α-syn can play different roles and interact with several proteins, including amyloid-beta (Aβ) and tau, in Alzheimer's disease (AD) and other neurodegenerative disorders.
MAIN BODY
In previous studies, α-syn aggregates in AD brains suggested a close relationship between AD and α-syn. In addition, α-syn directly interacts with Aβ and tau, promoting mutual aggregation and exacerbating the cognitive decline. The interaction of α-syn with Aβ and tau presented different consequences depending on the structural forms of the proteins. In AD, α-syn and tau levels in CSF were both elevated and revealed a high positive correlation. Especially, the CSF α-syn concentration was significantly elevated in the early stages of AD. Therefore, it could be a diagnostic marker of AD and help distinguish AD from other neurodegenerative disorders by incorporating other biomarkers.
CONCLUSION
The overall physiological and pathophysiological functions, structures, and genetics of α-syn in AD are reviewed and summarized. The numerous associations of α-syn with Aβ and tau suggested the significance of α-syn, as a partner of the pathophysiological roles in AD. Understanding the involvements of α-syn in the pathology of Aβ and tau could help address the unresolved issues of AD. In particular, the current status of the CSF α-syn in AD recommends it as an additional biomarker in the panel for AD diagnosis.
Topics: Humans; Alzheimer Disease; alpha-Synuclein; tau Proteins; Amyloid beta-Peptides; Biomarkers
PubMed: 36587215
DOI: 10.1186/s13195-022-01150-0 -
Alzheimer's Research & Therapy Apr 2022The ability to understand emotions is often disturbed in patients with cognitive impairments. Right temporal lobe structures play a crucial role in emotional processing,...
BACKGROUND
The ability to understand emotions is often disturbed in patients with cognitive impairments. Right temporal lobe structures play a crucial role in emotional processing, especially the amygdala, temporal pole (TP), superior temporal sulcus (STS), and anterior cingulate (AC). Those regions are affected in early stages of Alzheimer´s disease (AD). The aim of our study was to evaluate emotional prosody recognition (EPR) in participants with amnestic mild cognitive impairment (aMCI) due to AD, AD dementia patients, and cognitively healthy controls and to measure volumes or thickness of the brain structures involved in this process. In addition, we correlated EPR score to cognitive impairment as measured by MMSE. The receiver operating characteristic (ROC) analysis was used to assess the ability of EPR tests to differentiate the control group from the aMCI and dementia groups.
METHODS
Eighty-nine participants from the Czech Brain Aging Study: 43 aMCI due to AD, 36 AD dementia, and 23 controls, underwent Prosody Emotional Recognition Test. This experimental test included the playback of 25 sentences with neutral meaning each recorded with different emotional prosody (happiness, sadness, fear, disgust, anger). Volume of the amygdala and thickness of the TP, STS, and rostral and caudal parts of AC (RAC and CAC) were measured using FreeSurfer algorithm software. ANCOVA was used to evaluate EPR score differences. ROC analysis was used to assess the ability of EPR test to differentiate the control group from the aMCI and dementia groups. The Pearson's correlation coefficients were calculated to explore relationships between EPR scores, structural brain measures, and MMSE.
RESULTS
EPR was lower in the dementia and aMCI groups compared with controls. EPR total score had high sensitivity in distinguishing between not only controls and patients, but also controls and aMCI, controls and dementia, and aMCI and dementia. EPR decreased with disease severity as it correlated with MMSE. There was a significant positive correlation of EPR and thickness of the right TP, STS, and bilateral RAC.
CONCLUSIONS
EPR is impaired in AD dementia and aMCI due to AD. These data suggest that the broad range of AD symptoms may include specific deficits in the emotional sphere which further complicate the patient's quality of life.
Topics: Alzheimer Disease; Cognitive Dysfunction; Emotions; Humans; Neuropsychological Tests; Quality of Life; Recognition, Psychology
PubMed: 35382868
DOI: 10.1186/s13195-022-00989-7 -
Stem Cells Translational Medicine Nov 2017
Topics: Alzheimer Disease; Animals; Humans
PubMed: 28949098
DOI: 10.1002/sctm.12217 -
Journal of Alzheimer's Disease : JAD 2018It is estimated that by the year 2050 there will be more than 1.5 billion people globally over the age of 65 years. Aging is associated with changes to a number of... (Review)
Review
It is estimated that by the year 2050 there will be more than 1.5 billion people globally over the age of 65 years. Aging is associated with changes to a number of different cellular processes which are driven by a variety of factors that contribute to the characteristic decline in function that is seen across multiple physiological domains/tissues in the elderly (including the brain). Importantly, aging is also the primary risk factor for the development of neurodegenerative disorders such as Alzheimer's disease. As such, there is an urgent need to provide a greater understanding of both the pathogenesis and treatment of these devastating neurodegenerative disorders. One of the key cellular processes that becomes dysregulated with age and participates both directly and indirectly in age-related dysfunction, is metal homeostasis and the neurochemistry of metalloproteins, the basic science of which has been extensively reviewed in the past. In this review, we will focus on the human clinical intervention trials that have been conducted over approximately the last four decades that have attempted to establish the efficacy of targeting metal ions in the treatment of AD.
Topics: Alzheimer Disease; Animals; Humans; Metals
PubMed: 29562528
DOI: 10.3233/JAD-170662 -
Journal of Alzheimer's Disease : JAD 2020Dementia has been described as the greatest global health challenge in the 21st Century on account of longevity gains increasing its incidence, escalating health and... (Review)
Review
BACKGROUND
Dementia has been described as the greatest global health challenge in the 21st Century on account of longevity gains increasing its incidence, escalating health and social care pressures. These pressures highlight ethical, social, and political challenges about healthcare resource allocation, what health improvements matter to patients, and how they are measured. This study highlights the complexity of the ethical landscape, relating particularly to the balances that need to be struck when allocating resources; when measuring and prioritizing outcomes; and when individual preferences are sought.
OBJECTIVE
Health outcome prioritization is the ranking in order of desirability or importance of a set of disease-related objectives and their associated cost or risk. We analyze the complex ethical landscape in which this takes place in the most common dementia, Alzheimer's disease.
METHODS
Narrative review of literature published since 2007, incorporating snowball sampling where necessary. We identified, thematized, and discussed key issues of ethical salience.
RESULTS
Eight areas of ethical salience for outcome prioritization emerged: 1) Public health and distributive justice, 2) Scarcity of resources, 3) Heterogeneity and changing circumstances, 4) Knowledge of treatment, 5) Values and circumstances, 6) Conflicting priorities, 7) Communication, autonomy and caregiver issues, and 8) Disclosure of risk.
CONCLUSION
These areas highlight the difficult balance to be struck when allocating resources, when measuring and prioritizing outcomes, and when individual preferences are sought. We conclude by reflecting on how tools in social sciences and ethics can help address challenges posed by resource allocation, measuring and prioritizing outcomes, and eliciting stakeholder preferences.
Topics: Alzheimer Disease; Delivery of Health Care; Humans; Outcome Assessment, Health Care
PubMed: 32716354
DOI: 10.3233/JAD-191300 -
Current Alzheimer Research 2018In the nineties, numerous studies began to highlight the problem of the increasing number of people with Alzheimer's disease in developed countries, especially in the... (Review)
Review
In the nineties, numerous studies began to highlight the problem of the increasing number of people with Alzheimer's disease in developed countries, especially in the context of demographic progress. At the same time, the 21st century is typical of the development of advanced technologies that penetrate all areas of human life. Digital devices, sensors, and intelligent applications are tools that can help seniors and allow better communication and control of their caregivers. The aim of the paper is to provide an up-to-date summary of the use of technological solutions for improving health and safety for people with Alzheimer's disease. Firstly, the problems and needs of senior citizens with Alzheimer's disease (AD) and their caregivers are specified. Secondly, a scoping review is performed regarding the technological solutions suggested to assist this specific group of patients. Works obtained from the following libraries are used in this scoping review: Web of Science, PubMed, Springer, ACM and IEEE Xplore. Four independent reviewers screened the identified records and selected relevant articles which were published in the period from 2007 to 2018. A total of 6,705 publications were selected. In all, 128 full papers were screened. Results obtained from the relevant studies were furthermore divided into the following categories according to the type and use of technologies: devices, processing, and activity recognition. The leading technological solution in the category of devices are wearables and ambient noninvasive sensors. The introduction and utilization of these technologies, however, bring about challenges in acceptability, durability, ease of use, communication, and power requirements. Furthermore, it needs to be pointed out that these technological solutions should be based on open standards.
Topics: Aging; Alzheimer Disease; Computer-Assisted Instruction; Humans; Wearable Electronic Devices
PubMed: 29701154
DOI: 10.2174/1567205015666180427124547 -
Journal of Alzheimer's Disease : JAD 2021Neurodegenerative diseases called tauopathies, such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson's disease, among... (Review)
Review
Neurodegenerative diseases called tauopathies, such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson's disease, among others, are characterized by the pathological processing and accumulation of tau protein. AD is the most prevalent neurodegenerative disease and is characterized by two lesions: neurofibrillary tangles (NFTs) and neuritic plaques. The presence of NFTs in the hippocampus and neocortex in early and advanced stages, respectively, correlates with the patient's cognitive deterioration. So far, no drugs can prevent, decrease, or limit neuronal death due to abnormal pathological tau accumulation. Among potential non-pharmacological treatments, physical exercise has been shown to stimulate the development of stem cells (SCs) and may be useful in early stages. However, this does not prevent neuronal death from the massive accumulation of NFTs. In recent years, SCs therapies have emerged as a promising tool to repopulate areas involved in cognition in neurodegenerative diseases. Unfortunately, protocols for SCs therapy are still being developed and the mechanism of action of such therapy remains unclear. In this review, we show the advances and limitations of SCs therapy. Finally, we provide a critical analysis of its clinical use for AD.
Topics: Alzheimer Disease; Amyloid; Government Regulation; Hippocampus; Humans; Neocortex; Neurofibrillary Tangles; Plaque, Amyloid; Stem Cells; tau Proteins
PubMed: 34633316
DOI: 10.3233/JAD-200863 -
Annals of Nutrition & Metabolism 2022The rapid worldwide increase in the incidence of Alzheimer's disease is associated with changing nutrition patterns. Recently, some articles have highlighted the link... (Review)
Review
BACKGROUND
The rapid worldwide increase in the incidence of Alzheimer's disease is associated with changing nutrition patterns. Recently, some articles have highlighted the link between Alzheimer's disease and dietary cholesterol. It was found that elevated levels of some of its fractions in the brain and circulation affect metabolism.
SUMMARY
Previous studies have considered the relationship between Alzheimer's disease and oxidized cholesterol molecules in the brain. To date, there are limited data available on the relationship between oxidized cholesterol in the brain and Alzheimer's disease. There is a link between a diet high in cholesterol and its oxidized forms, leading to hypercholesterolemia, which is one of significant risk factors of dementia, and Alzheimer's disease. Oxidized cholesterol can be absorbed in the small intestine and cross the blood-brain barrier, leading to increased inflammation and endogenous oxidative process. Animal-origin foods are sources of oxidized cholesterol, with cholesterol oxidation beginning already after slaughter and occurring during storage and processing.
KEY MESSAGES
High-heat food preparation and storage of cooked products in the refrigerator followed by subsequent heating may significantly increase the amount of oxidized cholesterol products. Therefore, a diet low in cholesterol oxidation products and high in plants with antioxidative properties seems to be most preventable and should be implemented as early as possible.
Topics: Alzheimer Disease; Animals; Brain; Cholesterol; Diet; Humans; Oxysterols
PubMed: 35545012
DOI: 10.1159/000520514 -
Journal of Alzheimer's Disease : JAD 2018The amyloid-β oligomer (AβO) hypothesis was introduced in 1998. It proposed that the brain damage leading to Alzheimer's disease (AD) was instigated by soluble,... (Review)
Review
The amyloid-β oligomer (AβO) hypothesis was introduced in 1998. It proposed that the brain damage leading to Alzheimer's disease (AD) was instigated by soluble, ligand-like AβOs. This hypothesis was based on the discovery that fibril-free synthetic preparations of AβOs were potent CNS neurotoxins that rapidly inhibited long-term potentiation and, with time, caused selective nerve cell death (Lambert et al., 1998). The mechanism was attributed to disrupted signaling involving the tyrosine-protein kinase Fyn, mediated by an unknown toxin receptor. Over 4,000 articles concerning AβOs have been published since then, including more than 400 reviews. AβOs have been shown to accumulate in an AD-dependent manner in human and animal model brain tissue and, experimentally, to impair learning and memory and instigate major facets of AD neuropathology, including tau pathology, synapse deterioration and loss, inflammation, and oxidative damage. As reviewed by Hayden and Teplow in 2013, the AβO hypothesis "has all but supplanted the amyloid cascade." Despite the emerging understanding of the role played by AβOs in AD pathogenesis, AβOs have not yet received the clinical attention given to amyloid plaques, which have been at the core of major attempts at therapeutics and diagnostics but are no longer regarded as the most pathogenic form of Aβ. However, if the momentum of AβO research continues, particularly efforts to elucidate key aspects of structure, a clear path to a successful disease modifying therapy can be envisioned. Ensuring that lessons learned from recent, late-stage clinical failures are applied appropriately throughout therapeutic development will further enable the likelihood of a successful therapy in the near-term.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Humans; Models, Neurological
PubMed: 29843241
DOI: 10.3233/JAD-179941