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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 -
American Journal of Alzheimer's Disease... Aug 2019Alzheimer's disease (AD), a neurological disorder, is as a complex chronic disease of brain cell death that usher to cognitive decline and loss of memory. Its prevalence... (Review)
Review
Alzheimer's disease (AD), a neurological disorder, is as a complex chronic disease of brain cell death that usher to cognitive decline and loss of memory. Its prevalence differs according to risk factors associated with it and necropsy performs vital role in its definite diagnosis. The stages of AD vary from preclinical to severe that proceeds to death of patient with no availability of treatment. Biomarker may be a biochemical change that can be recognized by different emerging technologies such as proteomics and metabolomics. Plasma biomarkers, 5-protein classifiers, are readily being used for the diagnosis of AD and can also predict its progression with a great accuracy, specificity, and sensitivity. In this review, upregulation or downregulation of few plasma proteins in patients with AD has also been discussed, when juxtaposed with control, and thus serves as potent biomarker in the diagnosis of AD.
Topics: Alzheimer Disease; Biomarkers; Humans
PubMed: 31072117
DOI: 10.1177/1533317519848239 -
Neurotherapeutics : the Journal of the... Jan 2022Alzheimer's disease is associated with impairments in emotional communication including comprehension and production of facial emotional expressions, comprehension of... (Review)
Review
Alzheimer's disease is associated with impairments in emotional communication including comprehension and production of facial emotional expressions, comprehension of affective prosody, and alexithymia. It is also associated with disorders of emotional experience including mood disorders (depression and anxiety), agitation/aggression, and psychosis. Agitation/aggression and psychosis are particularly disruptive, are associated with earlier institutionalization, and pose a major challenge to institutional management. Treatment of disorders of emotional experience has been primarily pharmacologic (reviewed here in detail) and has relied heavily on antipsychotic medications despite the small effect sizes demonstrated in a large number of randomized controlled trials and the prevalence of serious side effects associated with these drugs. Recent studies suggest that treatment with pimavanserin, an antipsychotic without activity at dopamine receptors, may represent an important advance for treatment of psychotic manifestations, even as the drug appears to pose significant risk. Dextromethorphan/quinidine may represent an important advance in the treatment of agitation/aggression. There is also compelling evidence that sleep disorders, which are common among patients with Alzheimer's disease and are readily treatable, may potentiate psychotic manifestations and agitation/aggression, but further studies are needed.
Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Humans; Psychotic Disorders
PubMed: 35013934
DOI: 10.1007/s13311-021-01172-w -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss,... (Review)
Review
Alzheimer's disease (AD) is a cumulative progressive neurodegenerative disease characterized mainly by impairment in cognitive functions accompanied by memory loss, disturbance in behavior and personality, and difficulties in learning. Although the main causes of AD pathogenesis are not fully understood yet, amyloid-β peptides and tau proteins are supposed to be responsible for AD onset and pathogenesis. Various demographic, genetic, and environmental risk factors are involved in AD onset and pathogenesis such as age, gender, several genes, lipids, malnutrition, and poor diet. Significant changes were observed in microRNA (miRNA) levels between normal and AD cases giving hope for a diagnostic procedure for AD through a simple blood test. As yet, only two classes of AD therapeutic drugs are approved by FDA. They are classified as acetylcholinesterase inhibitors and N-methyl-D-aspartate antagonists (NMDA). Unfortunately, they can only treat the symptoms but cannot cure AD or stop its progression. New therapeutic approaches were developed for AD treatment including acitretin due to its ability to cross blood-brain barrier in the brain of rats and mice and induce the expression of ADAM 10 gene, the α-secretase of human amyloid-β protein precursor, stimulating the non-amyloidogenic pathway for amyloid-β protein precursor processing resulting in amyloid-β reduction. Also stem cells may have a crucial role in AD treatment as they can improve cognitive functions and memory in AD rats through regeneration of damaged neurons. This review spotlights on promising diagnostic techniques such as miRNAs and therapeutic approaches such as acitretin and/or stem cells keeping in consideration AD pathogenesis, stages, symptoms, and risk factors.
Topics: Animals; Humans; Acitretin; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; MicroRNAs; Stem Cell Transplantation; Stem Cells; Disease Susceptibility
PubMed: 37212107
DOI: 10.3233/JAD-221298 -
Theranostics 2023Alzheimer's disease (AD) is the most common neurodegenerative disease, which severely threatens the health of the elderly and causes significant economic and social... (Review)
Review
Alzheimer's disease (AD) is the most common neurodegenerative disease, which severely threatens the health of the elderly and causes significant economic and social burdens. The causes of AD are complex and include heritable but mostly aging-related factors. The primary aging hallmarks include genomic instability, telomere wear, epigenetic changes, and loss of protein stability, which play a dominant role in the aging process. Although AD is closely associated with the aging process, the underlying mechanisms involved in AD pathogenesis have not been well characterized. This review summarizes the available literature about primary aging hallmarks and their roles in AD pathogenesis. By analyzing published literature, we attempted to uncover the possible mechanisms of aberrant epigenetic markers with related enzymes, transcription factors, and loss of proteostasis in AD. In particular, the importance of oxidative stress-induced DNA methylation and DNA methylation-directed histone modifications and proteostasis are highlighted. A molecular network of gene regulatory elements that undergoes a dynamic change with age may underlie age-dependent AD pathogenesis, and can be used as a new drug target to treat AD.
Topics: Humans; Aged; Alzheimer Disease; Neurodegenerative Diseases; Aging; Epigenesis, Genetic; DNA Methylation
PubMed: 36593969
DOI: 10.7150/thno.79535 -
International Journal of Molecular... Sep 2023This review is devoted to the problems of the common features linking metabolic disorders and type 2 diabetes with the development of Alzheimer's disease. The... (Review)
Review
This review is devoted to the problems of the common features linking metabolic disorders and type 2 diabetes with the development of Alzheimer's disease. The pathogenesis of Alzheimer's disease closely intersects with the mechanisms of type 2 diabetes development, and an important risk factor for both pathologies is aging. Common pathological mechanisms include both factors in the development of oxidative stress, neuroinflammation, insulin resistance, and amyloidosis, as well as impaired mitochondrial dysfunctions and increasing cell death. The currently available drugs for the treatment of type 2 diabetes and Alzheimer's disease have limited therapeutic efficacy. It is important to note that drugs used to treat Alzheimer's disease, in particular acetylcholinesterase inhibitors, show a positive therapeutic potential in the treatment of type 2 diabetes, while drugs used in the treatment of type 2 diabetes can also prevent a number of pathologies characteristic for Alzheimer's disease. A promising direction in the search for a strategy for the treatment of type 2 diabetes and Alzheimer's disease may be the creation of complex multi-target drugs that have neuroprotective potential and affect specific common targets for type 2 diabetes and Alzheimer's disease.
Topics: Humans; Alzheimer Disease; Diabetes Mellitus, Type 2; Acetylcholinesterase; Mitochondria; Oxidative Stress
PubMed: 37833898
DOI: 10.3390/ijms241914450 -
Neurotherapeutics : the Journal of the... Jan 2022The clinical presentation and the pathological processes underlying Alzheimer's disease (AD) can be very heterogeneous in severity, location, and composition including... (Review)
Review
The clinical presentation and the pathological processes underlying Alzheimer's disease (AD) can be very heterogeneous in severity, location, and composition including the amount and distribution of AB deposition and spread of neurofibrillary tangles in different brain regions resulting in atypical clinical patterns and the existence of distinct AD variants. Heterogeneity in AD may be related to demographic factors (such as age, sex, educational and socioeconomic level) and genetic factors, which influence underlying pathology, the cognitive and behavioral phenotype, rate of progression, the occurrence of neuropsychiatric features, and the presence of comorbidities (e.g., vascular disease, neuroinflammation). Heterogeneity is also manifest in the individual resilience to the development of neuropathology (brain reserve) and the ability to compensate for its cognitive and functional impact (cognitive and functional reserve). The variability in specific cognitive profiles and types of functional impairment may be associated with different progression rates, and standard measures assessing progression may not be equivalent for individual cognitive and functional profiles. Other factors, which may govern the presence, rate, and type of progression of AD, include the individuals' general medical health, the presence of specific systemic conditions, and lifestyle factors, including physical exercise, cognitive and social stimulation, amount of leisure activities, environmental stressors, such as toxins and pollution, and the effects of medications used to treat medical and behavioral conditions. These factors that affect progression are important to consider while designing a clinical trial to ensure, as far as possible, well-balanced treatment and control groups.
Topics: Alzheimer Disease; Brain; Disease Progression; Humans
PubMed: 35084721
DOI: 10.1007/s13311-022-01185-z -
The Journal of Prevention of... 2020
Topics: Alzheimer Disease; Clinical Trials as Topic; Drug Development; Humans
PubMed: 32236392
DOI: 10.14283/jpad.2020.12 -
Journal of Advanced Research Dec 2023Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary... (Review)
Review
BACKGROUND
Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau protein. However, how these features contribute to synaptic dysfunction and axonal loss remains unclear. While years of considerable effort have been devoted to gaining an improved understanding of this devastating disease, the unavailability of patient-derived tissues, considerable genetic heterogeneity, and lack of animal models that faithfully recapitulate human AD have hampered the development of effective treatment options. Ongoing progress in human induced pluripotent stem cell (hiPSC) technology has permitted the derivation of patient- and disease-specific stem cells with unlimited self-renewal capacity. These cells can differentiate into AD-affected cell types, which support studies of disease mechanisms, drug discovery, and the development of cell replacement therapies in traditional and advanced cell culture models.
AIM OF REVIEW
To summarize current hiPSC-based AD models, highlighting the associated achievements and challenges with a primary focus on neuron and synapse loss.
KEY SCIENTIFIC CONCEPTS OF REVIEW
We aim to identify how hiPSC models can contribute to understanding AD-associated synaptic dysfunction and axonal loss. hiPSC-derived neural cells, astrocytes, and microglia, as well as more sophisticated cellular organoids, may represent reliable models to investigate AD and identify early markers of AD-associated neural degeneration.
Topics: Animals; Humans; Alzheimer Disease; Induced Pluripotent Stem Cells; Amyloid beta-Peptides; Neurons; Synapses
PubMed: 36646419
DOI: 10.1016/j.jare.2023.01.006 -
International Journal of Biological... Jun 2024The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly,... (Review)
Review
The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly, this neurodegenerative disease shares several biological and pathophysiological features with cancer, including cell-cycle dysregulation, angiogenesis, mitochondrial dysfunction, protein misfolding, and DNA damage. However, the genetic factors contributing to the overlap in biological processes between cancer and AD have not been actively studied. In this review, we discuss the shared biological features of cancer and AD, the molecular targets of anticancer drugs, and therapeutic approaches. First, we outline the common biological features of cancer and AD. Second, we describe several anticancer drugs, their molecular targets, and their effects on AD pathology. Finally, we discuss how protein-protein interactions (PPIs), receptor inhibition, immunotherapy, and gene therapy can be exploited for the cure and management of both cancer and AD. Collectively, this review provides insights for the development of AD theragnostics based on cancer drugs and molecular targets.
Topics: Humans; Alzheimer Disease; Neoplasms; Antineoplastic Agents; Immunotherapy; Animals; Molecular Targeted Therapy; Genetic Therapy
PubMed: 38685540
DOI: 10.1016/j.ijbiomac.2024.131925