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Journal of Alzheimer's Disease : JAD 2023With the rapid aging of the global population, the prevalence of neurodegenerative diseases has become a significant concern, with Alzheimer's disease (AD) being the... (Review)
Review
With the rapid aging of the global population, the prevalence of neurodegenerative diseases has become a significant concern, with Alzheimer's disease (AD) being the most common. However, the clinical trials of many drugs targeting AD have failed due to the challenges posed by the blood-brain barrier (BBB), which makes intracerebral administration of drugs difficult. However, nanoparticles (NPs) may aid in the delivery of such drugs. NPs are materials with sizes between 1-100 nm that offer several advantages, such as improving biocompatibility, prolonging half-life, transporting large molecules, crossing the BBB to deliver to the central nervous system, and exhibiting good targeting ability. In addition to drug delivery, NPs also have excellent diagnostic potential, and multifunctional NPs can integrate the advantages of diagnosis, targeting, and treatment. This mini-review article provides an overview of NPs, including the composition of the carrier, strategies for crossing the BBB, and different targets of AD pathology, with the aim of providing guidance for the development prospects of NPs.
Topics: Humans; Alzheimer Disease; Nanoparticles; Blood-Brain Barrier; Drug Delivery Systems; Pharmaceutical Preparations
PubMed: 37807779
DOI: 10.3233/JAD-230098 -
Journal of Neuroscience Research Feb 2020Microglia are the innate immune cells of the brain, which maintain homeostasis by constantly scanning and surveying the environment with their highly ramified processes.... (Review)
Review
Microglia are the innate immune cells of the brain, which maintain homeostasis by constantly scanning and surveying the environment with their highly ramified processes. In order to exert this function, they need to phagocytose synapses as well as debris and dead cells, a process that is further amplified in pathological conditions. Importantly, it has been shown that microglia phagocytic capacity is altered in the course of neurodegenerative disease, for which aging is one of the highest risk factors. Thus, understanding how phagocytosis is impaired during aging is a priority for future research. Advances in this area are expected to significantly contribute to our understanding of normal cognition during aging, as well as changes that take place in age-associated neurodegenerative diseases. In this review, we will summarize the current knowledge on how phagocytosis is executed and affected by aging or in age-associated neurological disorders, such as Alzheimer's disease (AD). Furthermore, we will summarize both protective and deleterious consequences of altered phagocytosis in AD and where relevant in other neurodegenerative diseases.
Topics: Aging; Alzheimer Disease; Animals; Brain; Humans; Microglia; Phagocytosis
PubMed: 30942936
DOI: 10.1002/jnr.24419 -
Journal of Alzheimer's Disease : JAD 2017Alzheimer's disease (AD), the main form of dementia in the elderly, is the most common progressive neurodegenerative disease characterized by rapidly progressive... (Review)
Review
Alzheimer's disease (AD), the main form of dementia in the elderly, is the most common progressive neurodegenerative disease characterized by rapidly progressive cognitive dysfunction and behavior impairment. AD exhibits a considerable heritability and great advances have been made in approaches to searching the genetic etiology of AD. In AD genetic studies, methods have developed from classic linkage-based and candidate-gene-based association studies to genome-wide association studies (GWAS) and next generation sequencing (NGS). The identification of new susceptibility genes has provided deeper insights to understand the mechanisms underlying AD. In addition to searching novel genes associated with AD in large samples, the NGS technologies can also be used to shed light on the 'black matter' discovery even in smaller samples. The shift in AD genetics between traditional studies and individual sequencing will allow biomaterials of each patient as the central unit of genetic studies. This review will cover genetic findings in AD and consequences of AD genetic findings. Firstly, we will discuss the discovery of mutations in APP, PSEN1, PSEN2, APOE, and ADAM10. Then we will summarize and evaluate the information obtained from GWAS of AD. Finally, we will outline the efforts to identify rare variants associated with AD using NGS.
Topics: Alzheimer Disease; Animals; Humans
PubMed: 28505974
DOI: 10.3233/JAD-170062 -
Journal of Alzheimer's Disease : JAD 2015Currently available diagnostic tests have moved the field closer to early diagnosis of Alzheimer's disease (AD); however, a definitive diagnosis is made only with the... (Review)
Review
Currently available diagnostic tests have moved the field closer to early diagnosis of Alzheimer's disease (AD); however, a definitive diagnosis is made only with the development of clinical dementia and the presence of amyloid plaques and neurofibrillary tangles at autopsy. An ideal antemortem AD biomarker should satisfy the following criteria: the ability to diagnose AD with high sensitivity and specificity as confirmed by the gold standard of autopsy validation; the ability to detect early-stage disease and track the progression of AD; and monitor therapeutic efficacy. AD biomarker technologies currently under development include in vivo brain imaging with PET and MRI (i.e., imaging of amyloid plaques, biochemical assays in cerebrospinal fluid (CSF) and peripheral tissues. CSF biomarkers have received increased attention in the past decade. However, it is unclear whether these biomarkers are capable of early diagnosis of AD, prior to Aβ accumulation, or whether they can differentiate between AD and non-AD dementias. In addition, CSF biomarkers may not lend themselves to diagnostic screening of elderly patients, given the invasiveness of lumbar puncture, inter-laboratory variability in techniques and sample handling, and the circadian fluctuation of CSF components. Although commonly viewed as an abnormality of the brain, AD is a systemic disease with associated dysfunction in metabolic, oxidative, inflammatory, and biochemical pathways in peripheral tissues, such as the skin and blood cells. This has led researchers to investigate and develop assays of peripheral AD biomarkers (a few with high sensitivity and specificity) that require minimally invasive skin or blood samples.
Topics: Alzheimer Disease; Biomarkers; Humans
PubMed: 25374110
DOI: 10.3233/JAD-142262 -
Journal of Alzheimer's Disease : JAD Apr 2016Brain lipid homeostasis plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Aggregation of amyloid-β peptide is one of the major... (Review)
Review
Brain lipid homeostasis plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Aggregation of amyloid-β peptide is one of the major events in AD. The complex interplay between lipids and amyloid-β accumulation has been intensively investigated. The proportions of lipid components including phospholipids, sphingolipids, and cholesterol are roughly similar across different brain regions under physiological conditions. However, disruption of brain lipid homeostasis has been described in AD and implicated in disease pathogenesis. Moreover, studies suggest that analysis of lipid composition in plasma and cerebrospinal fluid could improve our understanding of the disease development and progression, which could potentially serve as disease biomarkers and prognostic indicators for AD therapies. Here, we summarize the functional roles of AD risk genes and lipid regulators that modulate brain lipid homeostasis including different lipid species, lipid complexes, and lipid transporters, particularly their effects on amyloid processing, clearance, and aggregation, as well as neuro-toxicities that contribute to AD pathogenesis.
Topics: Alzheimer Disease; Animals; Brain; Genetic Predisposition to Disease; Humans; Lipid Metabolism; Mitochondria
PubMed: 27128373
DOI: 10.3233/JAD-160169 -
Journal of Alzheimer's Disease : JAD 2021Amyloid-β (Aβ) peptides and hyperphosphorylated tau protein are the most important pathological markers of Alzheimer's disease (AD). Neuroinflammation and oxidative... (Review)
Review
Amyloid-β (Aβ) peptides and hyperphosphorylated tau protein are the most important pathological markers of Alzheimer's disease (AD). Neuroinflammation and oxidative stress are also involved in the development and pathological mechanism of AD. Hypoxia inducible factor-1α (HIF-1α) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. Emerging evidence has revealed HIF-1α as a potential medicinal target for neurodegenerative diseases. On the one hand, HIF-1α increases AβPP processing and Aβ generation by promoting β/γ-secretases and suppressing α-secretases, inactivates microglia and reduces their activity, contributes to microglia death and neuroinflammation, which promotes AD pathogenesis. On the other hand, HIF-1α could resist the toxic effect of Aβ, inhibits tau hyperphosphorylation and promotes microglial activation. In summary, this review focuses on the potential complex roles and the future perspectives of HIF-1α in AD, in order to provide references for seeking new drug targets and treatment methods for AD.
Topics: Alzheimer Disease; Animals; Humans; Hypoxia-Inducible Factor 1, alpha Subunit
PubMed: 33612545
DOI: 10.3233/JAD-201448 -
Journal of Alzheimer's Disease : JAD 2022
Topics: Alzheimer Disease; Animals; Astrocytes; Humans
PubMed: 34897096
DOI: 10.3233/JAD-215436 -
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 -
Journal of Alzheimer's Disease : JAD 2018Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to... (Review)
Review
Translational neuroscience integrates the knowledge derived by basic neuroscience with the development of new diagnostic and therapeutic tools that may be applied to clinical practice in neurological diseases. This information can be used to improve clinical trial designs and outcomes that will accelerate drug development, and to discover novel biomarkers which can be efficiently employed to early recognize neurological disorders and provide information regarding the effects of drugs on the underlying disease biology. Alzheimer's disease (AD) and prion disease are two classes of neurodegenerative disorders characterized by incomplete knowledge of the molecular mechanisms underlying their occurrence and the lack of valid biomarkers and effective treatments. For these reasons, the design of therapies that prevent or delay the onset, slow the progression, or improve the symptoms associated to these disorders is urgently needed. During the last few decades, translational research provided a framework for advancing development of new diagnostic devices and promising disease-modifying therapies for patients with prion encephalopathies and AD. In this review, we provide present evidence of how supportive can be the translational approach to the study of dementias and show some results of our preclinical studies which have been translated to the clinical application following the 'bed-to-bench-and-back' research model.
Topics: Alzheimer Disease; Animals; Humans; Prion Diseases; Translational Research, Biomedical
PubMed: 29172000
DOI: 10.3233/JAD-170770 -
Journal of Alzheimer's Disease : JAD 2018The Alzheimer center of the VU University Medical Center opened in 2000 and was initiated to combine both patient care and research. Together, to date, all patients... (Review)
Review
The Alzheimer center of the VU University Medical Center opened in 2000 and was initiated to combine both patient care and research. Together, to date, all patients forming the Amsterdam Dementia Cohort number almost 6,000 individuals. In this cohort profile, we provide an overview of the results produced based on the Amsterdam Dementia Cohort. We describe the main results over the years in each of these research lines: 1) early diagnosis, 2) heterogeneity, and 3) vascular factors. Among the most important research efforts that have also impacted patients' lives and/or the research field, we count the development of novel, easy to use diagnostic measures such as visual rating scales for MRI and the Amsterdam IADL Questionnaire, insight in different subgroups of AD, and findings on incidence and clinical sequelae of microbleeds. Finally, we describe in the outlook how our research endeavors have improved the lives of our patients.
Topics: Alzheimer Disease; Biomarkers; Brain; Cohort Studies; Early Diagnosis; Humans; Magnetic Resonance Imaging; Netherlands; Quality Improvement; Surveys and Questionnaires
PubMed: 29562540
DOI: 10.3233/JAD-170850