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Neurologia May 2018Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of... (Review)
Review
Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes.
Topics: Age of Onset; Aging; Alzheimer Disease; Humans
PubMed: 26546285
DOI: 10.1016/j.nrl.2015.08.002 -
Der Radiologe May 2015Alzheimer's disease is a progressive neurodegenerative disorder with characteristic neuropathological changes. It is the most common form of dementia. As a definitive...
Alzheimer's disease is a progressive neurodegenerative disorder with characteristic neuropathological changes. It is the most common form of dementia. As a definitive diagnosis requires a neuropathological examination, clinical criteria have been established for the diagnostics of a probable Alzheimer's disease. In addition to the articles in this issue that focus on the imaging of dementia, this article provides a brief overview of clinically relevant aspects of Alzheimer's disease.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Brain; Cognitive Dysfunction; Cross-Sectional Studies; Diagnosis, Differential; Diagnostic Imaging; Disease Progression; Humans; Mental Status Schedule; Middle Aged; Neuropsychological Tests
PubMed: 25957008
DOI: 10.1007/s00117-014-2796-2 -
Expert Review of Molecular Diagnostics Mar 2015Alzheimer's disease (AD), the most common form of dementia in western societies, is a pathologically and clinically heterogeneous disease with a strong genetic... (Review)
Review
Alzheimer's disease (AD), the most common form of dementia in western societies, is a pathologically and clinically heterogeneous disease with a strong genetic component. The recent advances in high-throughput genome technologies allowing for the rapid analysis of millions of polymorphisms in thousands of subjects has significantly advanced our understanding of the genomic underpinnings of AD susceptibility. During the last 5 years, genome-wide association and whole-exome- and whole-genome sequencing studies have mapped more than 20 disease-associated loci, providing insights into the molecular pathways involved in AD pathogenesis and hinting at potential novel therapeutic targets. This review article summarizes the challenges and opportunities of when using genomic information for the diagnosis and prognosis of AD.
Topics: Alzheimer Disease; Biomarkers; Computational Biology; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Genomics; Humans; Prognosis
PubMed: 25634383
DOI: 10.1586/14737159.2015.1002469 -
EBioMedicine Jul 2016
Topics: Alzheimer Disease; Animals; Biomarkers; Disease Management; Drug Discovery; Early Diagnosis; Humans
PubMed: 27412262
DOI: 10.1016/j.ebiom.2016.07.001 -
Current Neuropharmacology 2018Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid β peptides and the formation of neurofibrillary tangles (NFTs) in the brain. Mounting evidence also implicates sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD.
METHODS
This paper provides an overview of findings from both human and animal studies investigating the role of microglia and astrocytes in AD, and discusses potential avenues for therapeutic intervention.
RESULTS
Glial-mediated inflammation is a 'double-edged sword', performing both detrimental and beneficial functions in AD. Despite tremendous effort in elucidating the molecular and cellular mechanisms underlying AD pathology, to date, there is no treatment that could prevent or cure this disease. Current treatments are only useful in slowing down the progression of AD and helping patients manage some of their behavioral and cognitive symptoms.
CONCLUSION
A better understanding of the role of microglia and astrocytes in the regulation of AD pathology is needed as this could pave the way for new therapeutic strategies.
Topics: Alzheimer Disease; Animals; Astrocytes; Cognition Disorders; Cytokines; Humans; Mental Disorders; Microglia
PubMed: 28730967
DOI: 10.2174/1570159X15666170720095240 -
Nature Reviews. Neurology Nov 2021Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates pathological alterations in central and... (Review)
Review
Dysregulation of the immune system is a cardinal feature of Alzheimer disease (AD), and a considerable body of evidence indicates pathological alterations in central and peripheral immune responses that change over time. Considering AD as a systemic immune process raises important questions about how communication between the peripheral and central compartments occurs and whether this crosstalk represents a therapeutic target. We established a whitepaper workgroup to delineate the current status of the field and to outline a research prospectus for advancing our understanding of peripheral-central immune crosstalk in AD. To guide the prospectus, we begin with an overview of seminal clinical observations that suggest a role for peripheral immune dysregulation and peripheral-central immune communication in AD, followed by formative animal data that provide insights into possible mechanisms for these clinical findings. We then present a roadmap that defines important next steps needed to overcome conceptual and methodological challenges, opportunities for future interdisciplinary research, and suggestions for translating promising mechanistic studies into therapeutic interventions.
Topics: Alzheimer Disease; Animals; Humans; Immune System; Research
PubMed: 34522039
DOI: 10.1038/s41582-021-00549-x -
International Journal of Molecular... Sep 2020Apolipoprotein E () is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of... (Review)
Review
Apolipoprotein E () is the major cholesterol carrier in the brain, affecting various normal cellular processes including neuronal growth, repair and remodeling of membranes, synaptogenesis, clearance and degradation of amyloid β (Aβ) and neuroinflammation. In humans, the gene has three common allelic variants, termed E2, E3, and E4. is considered the strongest genetic risk factor for Alzheimer's disease (AD), whereas is neuroprotective. To perform its normal functions, apoE must be secreted and properly lipidated, a process influenced by the structural differences associated with apoE isoforms. Here we highlight the importance of lipidated apoE as well as the -lipidation targeted therapeutic approaches that have the potential to correct or prevent neurodegeneration. Many of these approaches have been validated using diverse cellular and animal models. Overall, there is great potential to improve the lipidated state of apoE with the goal of ameliorating -associated central nervous system impairments.
Topics: Alzheimer Disease; Animals; Apolipoproteins E; Humans; Lipids; Neuroprotective Agents
PubMed: 32882843
DOI: 10.3390/ijms21176336 -
Alzheimer's & Dementia : the Journal of... Dec 2018Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable... (Clinical Trial)
Clinical Trial Observational Study
Like virtually all age-related chronic diseases, late-onset Alzheimer's disease (AD) develops over an extended preclinical period and is associated with modifiable lifestyle and environmental factors. We hypothesize that multimodal interventions that address many risk factors simultaneously and are individually tailored to patients may help reduce AD risk. We describe a novel clinical methodology used to evaluate and treat patients at two Alzheimer's Prevention Clinics. The framework applies evidence-based principles of clinical precision medicine to tailor individualized recommendations, follow patients longitudinally to continually refine the interventions, and evaluate N-of-1 effectiveness (trial registered at ClinicalTrials.gov NCT03687710). Prior preliminary results suggest that the clinical practice of AD risk reduction is feasible, with measurable improvements in cognition and biomarkers of AD risk. We propose using these early findings as a foundation to evaluate the comparative effectiveness of personalized risk management within an international network of clinician researchers in a cohort study possibly leading to a randomized controlled trial.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Female; Humans; Male; Middle Aged; Precision Medicine; Risk Reduction Behavior
PubMed: 30446421
DOI: 10.1016/j.jalz.2018.08.004 -
Redox Biology Dec 2023Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and... (Review)
Review
Oxygen metabolism abnormality plays a crucial role in the pathogenesis of Alzheimer's disease (AD) via several mechanisms, including hypoxia, oxidative stress, and mitochondrial dysfunction. Hypoxia condition usually results from living in a high-altitude habitat, cardiovascular and cerebrovascular diseases, and chronic obstructive sleep apnea. Chronic hypoxia has been identified as a significant risk factor for AD, showing an aggravation of various pathological components of AD, such as amyloid β-protein (Aβ) metabolism, tau phosphorylation, mitochondrial dysfunction, and neuroinflammation. It is known that hypoxia and excessive hyperoxia can both result in oxidative stress and mitochondrial dysfunction. Oxidative stress and mitochondrial dysfunction can increase Aβ and tau phosphorylation, and Aβ and tau proteins can lead to redox imbalance, thus forming a vicious cycle and exacerbating AD pathology. Hyperbaric oxygen therapy (HBOT) is a non-invasive intervention known for its capacity to significantly enhance cerebral oxygenation levels, which can significantly attenuate Aβ aggregation, tau phosphorylation, and neuroinflammation. However, further investigation is imperative to determine the optimal oxygen pressure, duration of exposure, and frequency of HBOT sessions. In this review, we explore the prospects of oxygen metabolism in AD, with the aim of enhancing our understanding of the underlying molecular mechanisms in AD. Current research aimed at attenuating abnormalities in oxygen metabolism holds promise for providing novel therapeutic approaches for AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Oxygen; Neuroinflammatory Diseases; tau Proteins; Hypoxia
PubMed: 37956598
DOI: 10.1016/j.redox.2023.102955 -
Nutrients Jan 2021The microbiota-gut-brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and... (Review)
Review
The microbiota-gut-brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer's disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of "pro-inflammatory" gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.
Topics: Aged; Alzheimer Disease; Gastrointestinal Microbiome; Humans
PubMed: 33504065
DOI: 10.3390/nu13020361