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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 -
The Lancet. Neurology Nov 2012The concept of cognitive reserve provides an explanation for differences between individuals in susceptibility to age-related brain changes or pathology related to... (Review)
Review
The concept of cognitive reserve provides an explanation for differences between individuals in susceptibility to age-related brain changes or pathology related to Alzheimer's disease, whereby some people can tolerate more of these changes than others and maintain function. Epidemiological studies suggest that lifelong experiences, including educational and occupational attainment, and leisure activities in later life, can increase this reserve. For example, the risk of developing Alzheimer's disease is reduced in individuals with higher educational or occupational attainment. Reserve can conveniently be divided into two types: brain reserve, which refers to differences in the brain structure that may increase tolerance to pathology, and cognitive reserve, which refers to differences between individuals in how tasks are performed that might enable some people to be more resilient to brain changes than others. Greater understanding of the concept of cognitive reserve could lead to interventions to slow cognitive ageing or reduce the risk of dementia.
Topics: Aging; Alzheimer Disease; Animals; Cognitive Reserve; Humans
PubMed: 23079557
DOI: 10.1016/S1474-4422(12)70191-6 -
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 -
Neuroscience Bulletin Dec 2018Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD... (Review)
Review
Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Topics: Alzheimer Disease; Animals; Biomarkers; Biomedical Research; Disease Progression; Humans; Magnetic Resonance Imaging
PubMed: 29956105
DOI: 10.1007/s12264-018-0249-z -
Alzheimer's & Dementia : the Journal of... Sep 2018Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's... (Review)
Review
INTRODUCTION
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches.
METHODS
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.
RESULTS
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.
DISCUSSION
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
Topics: Alzheimer Disease; Animals; Gender Identity; Humans; Sex Characteristics
PubMed: 29907423
DOI: 10.1016/j.jalz.2018.04.008 -
Neurologic Clinics May 2017Early-onset Alzheimer disease (EOAD), with onset in individuals younger than 65 years, although overshadowed by the more common late-onset AD (LOAD), differs... (Review)
Review
Early-onset Alzheimer disease (EOAD), with onset in individuals younger than 65 years, although overshadowed by the more common late-onset AD (LOAD), differs significantly from LOAD. EOAD comprises approximately 5% of AD and is associated with delays in diagnosis, aggressive course, and age-related psychosocial needs. One source of confusion is that a substantial percentage of EOAD are phenotypic variants that differ from the usual memory-disordered presentation of typical AD. The management of EOAD is similar to that for LOAD, but special emphasis should be placed on targeting the specific cognitive areas involved and more age-appropriate psychosocial support and education.
Topics: Age of Onset; Alzheimer Disease; Disease Progression; Humans
PubMed: 28410659
DOI: 10.1016/j.ncl.2017.01.005 -
Seminars in Neurology Apr 2019Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research... (Review)
Review
Alzheimer's disease (AD) is the commonest neurodegenerative disease and the most frequent cause of dementia. It affects 30 million people worldwide. Current research criteria focus on biomarkers' status for amyloid and tau using positron emission tomography and cerebrospinal fluid analysis, independent of clinical status. Current epidemiological data, which mostly rely on biomarker-undetermined AD cases, have highlighted ApoE4 and age as the main risk factors. Rare autosomal dominant mutations also account for a small fraction of early-onset AD. The main clinical phenotype at presentation is the amnestic phenotype targeting episodic memory. This is followed by rarer phenotypes such as posterior cortical atrophy, logopenic variant of primary progressive aphasia, frontal variant AD, corticobasal syndrome, and other even rarer presentations mimicking language variants of frontotemporal dementia. Main differential diagnoses include hippocampal sclerosis with TDP-43, primary age-related tauopathy, argyrophilic grain disease, frontotemporal lobar degeneration, Lewy body disease, chronic traumatic encephalopathy as well as nondegenerative disorders such as cerebrovascular disease, chronic alcohol consumption, limbic encephalitis, medial temporal lobe epilepsy, and others. Co-occurrence of AD pathology with other neurodegenerative and vascular diseases is common and increases with age. This presents a challenge in current clinical practice due to a lack of reliable biomarkers for non-AD neurodegenerative diseases.
Topics: Alzheimer Disease; Humans
PubMed: 30925614
DOI: 10.1055/s-0039-1681041