-
Current Alzheimer Research 2017The dramatic increase in the population with dementia expected in the next decades is accompanied by the establishment of novel and innovated methods that will offer... (Review)
Review
OBJECTIVE
The dramatic increase in the population with dementia expected in the next decades is accompanied by the establishment of novel and innovated methods that will offer accurate and efficient detection of the disease in its early stages. While Alzheimer's disease is the most common cause of dementia, by the time it is typically diagnosed, substantial neuronal loss and neuropathological lesions can damage many brain regions. The aim of this study is to investigate the main risk factors that affect and increase Alzheimer's disease progression over time even in cases with no significant memory impairment present. Several potential markers are discussed such as oxidative stress, metal ions, vascular disorders, protein dysfunctions and alterations in the mitochondrial populations.
CONCLUSION
A multiparametric model of Alzheimer's biomarkers is presented according to the latest classification of the disease.
Topics: Alzheimer Disease; Biomarkers; Humans
PubMed: 28164766
DOI: 10.2174/1567205014666170203125942 -
The Lancet. Neurology Mar 2021Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes... (Review)
Review
Most patients with Alzheimer's disease present with amnestic problems; however, a substantial proportion, over-represented in young-onset cases, have atypical phenotypes including predominant visual, language, executive, behavioural, or motor dysfunction. In the past, these individuals often received a late diagnosis; however, availability of CSF and PET biomarkers of Alzheimer's disease pathologies and incorporation of atypical forms of Alzheimer's disease into new diagnostic criteria increasingly allows them to be more confidently diagnosed early in their illness. This early diagnosis in turn allows patients to be offered tailored information, appropriate care and support, and individualised treatment plans. These advances will provide improved access to clinical trials, which often exclude atypical phenotypes. Research into atypical Alzheimer's disease has revealed previously unrecognised neuropathological heterogeneity across the Alzheimer's disease spectrum. Neuroimaging, genetic, biomarker, and basic science studies are providing key insights into the factors that might drive selective vulnerability of differing brain networks, with potential mechanistic implications for understanding typical late-onset Alzheimer's disease.
Topics: Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Female; Humans; Male; Middle Aged; Neuroimaging
PubMed: 33609479
DOI: 10.1016/S1474-4422(20)30440-3 -
International Journal of Molecular... Dec 2022Alzheimer's disease (AD) is the most common type of dementia, accounting for 60% to 80% of all cases [...].
Alzheimer's disease (AD) is the most common type of dementia, accounting for 60% to 80% of all cases [...].
Topics: Humans; Alzheimer Disease
PubMed: 36613544
DOI: 10.3390/ijms24010107 -
Clinical Medicine (London, England) Jun 2016Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms... (Review)
Review
Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy.
Topics: Alzheimer Disease; Amyloid; Cholinesterase Inhibitors; Humans; Neuroprotective Agents
PubMed: 27251914
DOI: 10.7861/clinmedicine.16-3-247 -
Zoological Research Nov 2022Although great advances in elucidating the molecular basis and pathogenesis of Alzheimer's disease (AD) have been made and multifarious novel therapeutic approaches have... (Review)
Review
Although great advances in elucidating the molecular basis and pathogenesis of Alzheimer's disease (AD) have been made and multifarious novel therapeutic approaches have been developed, AD remains an incurable disease. Evidence shows that AD neuropathology occurs decades before clinical presentation. AD is divided into three stages: preclinical stage, mild cognitive impairment (MCI), and AD dementia. In the natural world, some animals, such as non-human primates (NHPs) and canines, can develop spontaneous AD-like dementia. However, most animals do not develop AD. With the development of transgenic techniques, both invertebrate and vertebrate animals have been employed to uncover the mechanisms of AD and study treatment methods. Most AD research focuses on early-onset familial AD (FAD) because FAD is associated with specific genetic mutations. However, there are no well-established late-onset sporadic AD (SAD) animal models because SAD is not directly linked to any genetic mutation, and multiple environmental factors are involved. Moreover, the widely used animal models are not able to sufficiently recapitulate the pathological events that occur in the MCI or preclinical stages. This review summarizes the common models used to study AD, from yeast to NHP models, and discusses the different applications, evaluation methods, and challenges related to AD animal models, as well as prospects for the evolution of future studies.
Topics: Animals; Dogs; Alzheimer Disease; Disease Models, Animal; Dog Diseases; Mutation
PubMed: 36317468
DOI: 10.24272/j.issn.2095-8137.2022.289 -
International Journal of Molecular... Mar 2023Alzheimer's disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is... (Review)
Review
Alzheimer's disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer's disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer's disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.
Topics: Humans; Alzheimer Disease; Inflammation; Neuritis
PubMed: 37047492
DOI: 10.3390/ijms24076518 -
Nature Reviews. Neurology Jul 2018Alzheimer disease (AD) is the most common form of dementia. Pathologically, AD is characterized by amyloid plaques and neurofibrillary tangles in the brain, with... (Review)
Review
Alzheimer disease (AD) is the most common form of dementia. Pathologically, AD is characterized by amyloid plaques and neurofibrillary tangles in the brain, with associated loss of synapses and neurons, resulting in cognitive deficits and eventually dementia. Amyloid-β (Aβ) peptide and tau protein are the primary components of the plaques and tangles, respectively. In the decades since Aβ and tau were identified, development of therapies for AD has primarily focused on Aβ, but tau has received more attention in recent years, in part because of the failure of various Aβ-targeting treatments in clinical trials. In this article, we review the current status of tau-targeting therapies for AD. Initially, potential anti-tau therapies were based mainly on inhibition of kinases or tau aggregation, or on stabilization of microtubules, but most of these approaches have been discontinued because of toxicity and/or lack of efficacy. Currently, the majority of tau-targeting therapies in clinical trials are immunotherapies, which have shown promise in numerous preclinical studies. Given that tau pathology correlates better with cognitive impairments than do Aβ lesions, targeting of tau is expected to be more effective than Aβ clearance once the clinical symptoms are evident. With future improvements in diagnostics, these two hallmarks of the disease might be targeted prophylactically.
Topics: Alzheimer Disease; Animals; Humans; tau Proteins
PubMed: 29895964
DOI: 10.1038/s41582-018-0013-z -
Nature Reviews. Neurology Sep 2019Polymorphism in the apolipoprotein E (APOE) gene is a major genetic risk determinant of late-onset Alzheimer disease (AD), with the APOE*ε4 allele conferring an... (Review)
Review
Polymorphism in the apolipoprotein E (APOE) gene is a major genetic risk determinant of late-onset Alzheimer disease (AD), with the APOE*ε4 allele conferring an increased risk and the APOE*ε2 allele conferring a decreased risk relative to the common APOE*ε3 allele. Strong evidence from clinical and basic research suggests that a major pathway by which APOE4 increases the risk of AD is by driving earlier and more abundant amyloid pathology in the brains of APOE*ε4 carriers. The number of amyloid-β (Aβ)-dependent and Aβ-independent pathways that are known to be differentially modulated by APOE isoforms is increasing. For example, evidence is accumulating that APOE influences tau pathology, tau-mediated neurodegeneration and microglial responses to AD-related pathologies. In addition, APOE4 is either pathogenic or shows reduced efficiency in multiple brain homeostatic pathways, including lipid transport, synaptic integrity and plasticity, glucose metabolism and cerebrovascular function. Here, we review the recent progress in clinical and basic research into the role of APOE in AD pathogenesis. We also discuss how APOE can be targeted for AD therapy using a precision medicine approach.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Apolipoproteins E; Brain; Genetic Predisposition to Disease; Humans; Plaque, Amyloid; Polymorphism, Genetic
PubMed: 31367008
DOI: 10.1038/s41582-019-0228-7 -
Tidsskrift For Den Norske Laegeforening... May 2021Alzheimer's disease is the most common cause of dementia globally. Its prevalence will increase considerably in the years to come, in pace with the increasing proportion...
Alzheimer's disease is the most common cause of dementia globally. Its prevalence will increase considerably in the years to come, in pace with the increasing proportion of older people. No disease-modifying treatment is currently available. Measures to mitigate risk in mid-life may potentially prevent or postpone up to 40 % of dementia cases at group level.
Topics: Aged; Alzheimer Disease; Humans
PubMed: 33950641
DOI: 10.4045/tidsskr.20.0919 -
The Journal of Prevention of... 2018Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD... (Review)
Review
Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Commonly characterized as ending in reproductive senescence, many symptoms of MT are neurological, including disruption of estrogen-regulated systems such as thermoregulation, sleep, and circadian rhythms, as well as depression and impairment in multiple cognitive domains. Preclinical studies have shown that, during MT, the estrogen network uncouples from the brain bioenergetic system. The resulting hypometabolic state could serve as the substrate for neurological dysfunction. Indeed, translational brain imaging studies demonstrate that 40-60 year-old perimenopausal and postmenopausal women exhibit an AD-endophenotype characterized by decreased metabolic activity and increased brain amyloid-beta deposition as compared to premenopausal women and to age-matched men. This review discusses the MT as a window of opportunity for therapeutic interventions to compensate for brain bioenergetic crisis and combat the subsequent increased risk for AD in women.
Topics: Alzheimer Disease; Brain; Female; Hormone Replacement Therapy; Humans; Menopause; Risk Factors
PubMed: 30298180
DOI: 10.14283/jpad.2018.34