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Medicina (Kaunas, Lithuania) Jul 2020Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature... (Review)
Review
Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature focusing on Alzheimer's disease cardinal cognitive features, autonomic nervous system dysfunction remains understudied despite being common in the elderly. In this article, we reviewed the evidence for autonomic nervous system involvement in Alzheimer's disease. We identified four major potential causes for dysautonomia in Alzheimer's disease, out of which two are well-studied (comorbidities and medication) and two are rather hypothetical (Alzheimer's pathology and brain co-pathology). Although there appears to be some evidence linking Alzheimer's disease pathology to autonomic nervous system dysfunction, there is an important gap between two types of studies; histopathologic studies do not address dysautonomia manifestations, whereas clinical studies do not employ histopathologic diagnostic confirmation. Moreover, brain co-pathology is emerging as an important confounding factor. Therefore, we consider the correlation between dysautonomia and Alzheimer's disease to be an open question that needs further study. Nevertheless, given its impact on morbidity and mortality, we emphasize the importance of assessing autonomic dysfunction in patients with Alzheimer clinical syndrome.
Topics: Aged; Alzheimer Disease; Female; Humans; Male; Primary Dysautonomias
PubMed: 32650427
DOI: 10.3390/medicina56070337 -
CNS Neuroscience & Therapeutics Dec 2023The systematic molecular associations between the peripheral blood cells and brain in Alzheimer's disease (AD) remains unclear, which hinders our understanding of AD...
BACKGROUND
The systematic molecular associations between the peripheral blood cells and brain in Alzheimer's disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers.
METHODS
Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD.
RESULTS
By bioinformatics analysis, a total of 243 genes were differentially expressed in the central and peripheral systems, mainly enriched in three modules: immune response, glucose metabolism and lysosome. In addition, lysosome related gene ATP6V1E1 and immune response related genes (IL2RG, OSM, EVI2B TNFRSF1A, CXCR4, STAT5A) were significantly correlated with Aβ or Tau pathology. Finally, receiver operating characteristic (ROC) analysis revealed that ATP6V1E1 showed high-diagnostic potential for AD.
CONCLUSION
Taken together, our data identified the main pathological pathways in AD progression, particularly the systemic dysregulation of the immune response, and provided peripheral biomarkers for AD diagnosis.
Topics: Humans; Alzheimer Disease; Transcriptome; Brain; Biomarkers
PubMed: 37334737
DOI: 10.1111/cns.14316 -
Journal of Alzheimer's Disease : JAD 2022Although the cause(s) of Alzheimer's disease in the majority of cases remains elusive, it has long been associated with hypertension. In animal models of the disease,... (Review)
Review
Although the cause(s) of Alzheimer's disease in the majority of cases remains elusive, it has long been associated with hypertension. In animal models of the disease, hypertension has been shown to exacerbate Alzheimer-like pathology and behavior, while in humans, hypertension during mid-life increases the risk of developing the disease later in life. Unfortunately, once individuals are diagnosed with the disease, there are few therapeutic options available. There is neither an effective symptomatic treatment, one that treats the debilitating cognitive and memory deficits, nor, more importantly, a neuroprotective treatment, one that stops the relentless progression of the pathology. Further, there is no specific preventative treatment that offsets the onset of the disease. A key factor or clue in this quest for an effective preventative and therapeutic treatment may lie in the contribution of hypertension to the disease. In this review, we explore the idea that photobiomodulation, the application of specific wavelengths of light onto body tissues, can reduce the neuropathology and behavioral deficits in Alzheimer's disease by controlling hypertension. We suggest that treatment with photobiomodulation can be an effective preventative and therapeutic option for this neurodegenerative disease.
Topics: Animals; Humans; Alzheimer Disease; Neurodegenerative Diseases; Hypertension; Disease Models, Animal
PubMed: 36189597
DOI: 10.3233/JAD-220632 -
Zoological Research Nov 2023Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss. Emerging evidence suggests that... (Review)
Review
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss. Emerging evidence suggests that autophagy plays an important role in the pathogenesis of AD through the regulation of amyloid-beta (Aβ) and tau metabolism, and that autophagy dysfunction exacerbates amyloidosis and tau pathology. Therefore, targeting autophagy may be an effective approach for the treatment of AD. Animal models are considered useful tools for investigating the pathogenic mechanisms and therapeutic strategies of diseases. This review aims to summarize the pathological alterations in autophagy in representative AD animal models and to present recent studies on newly discovered autophagy-stimulating interventions in animal AD models. Finally, the opportunities, difficulties, and future directions of autophagy targeting in AD therapy are discussed.
Topics: Animals; Alzheimer Disease; Amyloid beta-Peptides; Autophagy; Models, Animal
PubMed: 37963840
DOI: 10.24272/j.issn.2095-8137.2023.294 -
Neurobiology of Aging Nov 2023Sporadic Alzheimer's disease and cancer remain epidemiologically inversely related, and exploring the reverse pathogenesis is important for our understanding of both.... (Review)
Review
Sporadic Alzheimer's disease and cancer remain epidemiologically inversely related, and exploring the reverse pathogenesis is important for our understanding of both. Cognitive dysfunctions in Alzheimer's disease (AD) might result from the depletion of adaptive reserves in the brain. Energy storage in the brain is limited and is dynamically regulated by neurovascular and neurometabolic coupling. The research on neurodegenerative diseases has been dominated by the neurocentric view that neuronal defects cause the diseases. However, the proposal of the 2-hit vascular hypothesis in AD led us to focus on alterations in the vasculature, especially hypoperfusion. Chronic hypoxia is a feature shared by AD and cancer. It is interesting how contradicting chronic hypoxia's effects on both cancer and AD are. In this article, we discuss the potential links between the 2 diseases' etiology, from comparable upstream circumstances to diametrically opposed downstream effects. We suggest opposing potential mechanisms, including upregulation and downregulation of hypoxia-inducible factor-1α, the Warburg and reverse-Warburg effects, lactate-mediated intracellular acidic and alkaline conditions, and VDAC1-mediated apoptosis and antiapoptosis, and search for regulators that may be identified as the crossroads between cancer and AD.
Topics: Humans; Alzheimer Disease; Brain; Hypoxia; Neoplasms
PubMed: 37572528
DOI: 10.1016/j.neurobiolaging.2023.07.002 -
International Journal of Molecular... Jan 2022The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs)... (Review)
Review
The cell cycle consists of successive events that lead to the generation of new cells. The cell cycle is regulated by different cyclins, cyclin-dependent kinases (CDKs) and their inhibitors, such as p27. At the nuclear level, p27 has the ability to control the evolution of different phases of the cell cycle and oppose cell cycle progression by binding to CDKs. In the cytoplasm, diverse functions have been described for p27, including microtubule remodeling, axonal transport and phagocytosis. In Alzheimer's disease (AD), alterations to cycle events and a purported increase in neurogenesis have been described in the early disease process before significant pathological changes could be detected. However, most neurons cannot progress to complete their cell division and undergo apoptotic cell death. Increased levels of both the p27 levels and phosphorylation status have been described in AD. Increased levels of Aβ42, tau hyperphosphorylation or even altered insulin signals could lead to alterations in p27 post-transcriptional modifications, causing a disbalance between the levels and functions of p27 in the cytoplasm and nucleus, thus inducing an aberrant cell cycle re-entry and alteration of extra cell cycle functions. Further studies are needed to completely understand the role of p27 in AD and the therapeutic opportunities associated with the modulation of this target.
Topics: Alzheimer Disease; Animals; Cell Cycle; Cyclin-Dependent Kinase Inhibitor p27; Humans; Protein Processing, Post-Translational
PubMed: 35163135
DOI: 10.3390/ijms23031211 -
Translational Neurodegeneration Jan 2024Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that... (Review)
Review
Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.
Topics: Animals; Humans; Alzheimer Disease; Amyloid beta-Peptides; Aging; Brain; Memory Disorders
PubMed: 38254235
DOI: 10.1186/s40035-024-00397-x -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Mar 2022Alzheimer's disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious... (Review)
Review
Alzheimer's disease (AD) is a common neurodegenerative disease. In an aging society, the high prevalence of AD and the low quality of life of AD patients create serious problems for individuals, families and the society. However, the etiology and pathogenesis of AD are still not fully understood. Age, genetics, environment and other factors are all relevant to AD, and treatment has not achieved satisfactory results. Recent studies have found that oral dysbiosis is closely related to the pathogenesis of AD, and that oral bacterial infection may be one of the causes of AD. Oral cavity is the largest microbial ecosystem of human body, and its homeostasis is critical to health. Bacterial infections caused by oral dysbiosis can directly and indirectly induce the metabolic imbalance of amyloid β-protein (Aβ) in the brain and the hyperphosphorylation of Tau protein. Then, the precipitation forms senile plaques and neurofibrillary tangles (NFTs) that damage neurons. Based on the latest research findings, we herein discussed the correlation between oral microbiota and the pathogenesis of AD and the mechanisms involved, as well as the pathogenic mechanism of main oral bacteria. In addition, we explored the potential application prospects of oral microbiota-targeted therapy.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Humans; Microbiota; Neurodegenerative Diseases; Quality of Life
PubMed: 35332717
DOI: 10.12182/20220360304 -
Alzheimer's Research & Therapy Oct 2023Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is... (Review)
Review
BACKGROUND
Alterations in mitochondrial DNA (mtDNA) levels have been observed in Alzheimer's disease and are an area of research that shows promise as a useful biomarker. It is well known that not only are the mitochondria a key player in producing energy for the cell, but they also are known to interact in other important intracellular processes as well as extracellular signaling and communication. BODY: This mini review explores how cells use mtDNA as a stress signal, particularly in Alzheimer's disease. We investigate the measurement of these mtDNA alterations, the mechanisms of mtDNA release, and the immunological effects from the release of these stress signals.
CONCLUSION
Literature indicates a correlation between the release of mtDNA in Alzheimer's disease and increased immune responses, showing promise as a potential biomarker. However, several questions remain unanswered and there is great potential for future studies in this area.
Topics: Humans; DNA, Mitochondrial; Alzheimer Disease; Mitochondria; Signal Transduction; Biomarkers; Oxidative Stress
PubMed: 37821944
DOI: 10.1186/s13195-023-01322-6 -
Genes Nov 2021Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ)...
Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ) and tau proteins in the brain, loss of gray matter, and neuronal death [...].
Topics: Alzheimer Disease; Animals; Humans
PubMed: 34828400
DOI: 10.3390/genes12111794