Abstract:
:Most therapeutic agents are designed to target a molecule or pathway without consideration of the mechanisms involved in the physiological turnover or removal of that target. In light of this and in particular for Alzheimer's disease, a number of therapeutic interventions are presently being developed/investigated which target the amyloid-β peptide (Aβ). However, the literature has not adequately considered which Aβ physiological clearance pathways are necessary and sufficient for the effective action of these therapeutics. In this review, we evaluate the therapeutic strategies targeting Aβ presently in clinical development, discuss the possible interaction of these treatments with pathways that under normal physiological conditions are responsible for the turnover of Aβ and highlight possible caveats. We consider immunization strategies primarily reliant on a peripheral sink mechanism of action, small molecules that are reliant on entry into the CNS and thus degradation pathways within the brain, as well as lifestyle interventions that affect vascular, parenchymal and peripheral degradation pathways. We propose that effective development of Alzheimer's disease therapeutic strategies targeting Aβ peptide will require consideration of the age- and disease-specific changes to endogenous Aβ clearance mechanisms in order to elicit maximal efficacy.
journal_name
Front Aging Neuroscijournal_title
Frontiers in aging neuroscienceauthors
Morrone CD,Liu M,Black SE,McLaurin Jdoi
10.3389/fnagi.2015.00064subject
Has Abstractpub_date
2015-05-05 00:00:00pages
64issn
1663-4365journal_volume
7pub_type
杂志文章,评审abstract::Despite varied etiologies and symptoms, several neurodegenerative diseases-specifically, Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HDs)-share the common feature of abnormal circadian rhythms, such as those in behavior (e.g., disrupted sleep/wake cycles), physiological processes (e.g., diminished h...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2017.00170
更新日期:2017-05-30 00:00:00
abstract:INTRODUCTION:Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2013.00092
更新日期:2013-12-16 00:00:00
abstract::More than 95% of Alzheimer's disease (AD) belongs to sporadic AD (sAD), and related animal models are the important research tools for investigating the pathogenesis and developing new drugs for sAD. An intracerebroventricular infusion of streptozotocin (ICV-STZ) is commonly employed to generate sporadic AD animal mod...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00347
更新日期:2017-10-31 00:00:00
abstract::Electroacupuncture (EA) has been reported to have beneficial effects on Alzheimer's disease (AD). BACE1 (β-site amyloid precursor protein-cleaving enzyme 1) is involved in the abnormal production of amyloid-β plaque (Aβ), a hallmark of AD pathophysiology. Thus, the present study investigated the effects of EA on memor...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00148
更新日期:2015-07-29 00:00:00
abstract::Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2017.00129
更新日期:2017-05-03 00:00:00
abstract::Alzheimer's disease (AD) and treatment of the brain in aging require the development of new biologic drugs, such as recombinant proteins or gene therapies. Biologics are large molecule therapeutics that do not cross the blood-brain barrier (BBB). BBB drug delivery is the limiting factor in the future development of ne...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00373
更新日期:2020-01-10 00:00:00
abstract::This internal representation of movement of part(s) of the body is involved during Implicit Motor Imagery tasks (IMI); the same representations are employed in the laterality judgment task. Few studies have looked at the consequences of aging, Alzheimer's disease (AD) and mild cognitive impairment (MCI) on the process...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00238
更新日期:2015-12-23 00:00:00
abstract::Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer's disease (AD). Inconsistent results about the role of APOE ε4 alleles on cognitive decline of community non-dementia elderly have been reported. This study aimed to examine the relationship between APOE ε4 allele and cognitive abilities...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00071
更新日期:2019-03-29 00:00:00
abstract::Dietary folic acid deficiency induced early hearing loss in C57BL/6J mice after 2-months, corroborates the epidemiological association previously described between vitamin deficiency and this sensory impairment. However, this strain is prone to early hearing loss, and hence we decided to analyze whether the effects ex...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00209
更新日期:2016-08-31 00:00:00
abstract::Background: Leisure-time physical activity (PA) has been proposed as a protective factor against dementia, whereas psychological distress is associated with an increased risk of dementia. We investigated the associations of leisure-time PA and psychological distress with dementia-related mortality, and whether the ass...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00151
更新日期:2018-05-25 00:00:00
abstract::Alzheimer's disease treatment is still an open problem. The diversity of symptoms, the alterations in common pathophysiology, the existence of asymptomatic cases, the different types of sporadic and familial Alzheimer's and their relevance with other types of dementia and comorbidities, have already created a myth-fea...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00077
更新日期:2017-03-31 00:00:00
abstract::Hypertension has a profound influence on the structure and function of blood vessels. Cerebral vessels undergo both structural and functional changes in hypertensive animals. However, dynamic changes of cerebrovasculature and the factors involved in this process are largely unknown. In this study, we explored the dyna...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00359
更新日期:2017-11-02 00:00:00
abstract::Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. It begins years prior to the onset of clinical symptoms, such as memory loss and cognitive decline. Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron,...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2014.00091
更新日期:2014-05-15 00:00:00
abstract::Background: Decreased bone mineral density (BMD) was associated with poorer cognitive function and increased risk of Alzheimer's disease (AD). However, objective evidence for the relationship between osteoporosis and AD in humans has not been extensively described. Objectives: We aimed to evaluate the relationships be...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.00178
更新日期:2020-06-17 00:00:00
abstract::Neurofilament light (NFL) is a putative biomarker of neurodegeneration. This study evaluates the correlative association of NFL with Alzheimer's disease (AD) indices. Relevant studies were identified after a literature search in electronic databases and study selection was based on pre-determined eligibility criteria....
journal_title:Frontiers in aging neuroscience
pub_type:
doi:10.3389/fnagi.2019.00254
更新日期:2019-09-13 00:00:00
abstract::This paper seeks to present a new perspective on the aging brain. Here, we make connections between two key phenomena of brain aging: (1) increased neural noise or random background activity; and (2) slowing of brain activity. Our perspective proposes the possibility that the slowing of neural processing due to decrea...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2012.00027
更新日期:2012-09-25 00:00:00
abstract::Introduction: Falling is one of the primary concerns for people with Parkinson's Disease and occurs predominately during dynamic movements, such as walking. Several methods have been proposed to quantify dynamic balance and to assess fall risk. However, no consensus has been reached concerning which method is most app...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00387
更新日期:2018-11-22 00:00:00
abstract:Background:Age-related cognitive decline begins in middle age and persists with age. Leukocyte telomere length (LTL) decreases with age and is enhanced by inflammation and oxidative stress. However, whether shorter LTL correlates with cognitive decline remains controversial. Aims:We aimed to investigate the relationsh...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.527658
更新日期:2020-10-30 00:00:00
abstract::Background and Purpose: This study aimed to investigate the association between insulin resistance (IR) and the overall cerebral small vessel disease (CSVD) burden. Methods: We recruited elderly, nondiabetic, healthy subjects prospectively. The overall effect of CSVD on the brain was described by a validated CSVD scor...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00127
更新日期:2019-06-12 00:00:00
abstract::Delirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent m...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00107
更新日期:2014-06-10 00:00:00
abstract::Aging is associated with cognitive decline and alterations in early perceptual processes. Studies in the auditory and visual sensory modalities have shown that the mismatch negativity [or the mismatch response (MMR)], an event-related potential (ERP) elicited by a deviant stimulus in a background of homogenous events,...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00293
更新日期:2014-10-27 00:00:00
abstract::The obesity epidemic had spawned considerable interest in understanding peoples' responses to palatable food cues that are plentiful in obesogenic environments. In this paper we examine how trait mindfulness of older, obese adults may moderate brain networks that arise from exposure to such cues. Nineteen older, obese...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2012.00013
更新日期:2012-06-06 00:00:00
abstract::Manganese (Mn) is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinson...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2013.00023
更新日期:2013-06-24 00:00:00
abstract::Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregu...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2013.00044
更新日期:2013-08-23 00:00:00
abstract::Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipe...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00028
更新日期:2018-02-12 00:00:00
abstract::Background: Hypersensitivity to general anesthetics may predict poor postoperative outcomes, especially among the older subjects. Therefore, it is essential to elucidate the mechanism underlying hypersensitivity to volatile anesthetics in the aging population. Given the fact that isoflurane sensitivity increases with ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.583542
更新日期:2020-12-03 00:00:00
abstract::Background: Primary progressive aphasia (PPA) is a clinical syndrome characterized by the neurodegeneration of language brain systems. Three main clinical forms (non-fluent, semantic, and logopenic PPA) have been recognized, but applicability of the classification and the capacity to predict the underlying pathology i...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00230
更新日期:2018-07-31 00:00:00
abstract::Many cognitive abilities decline with aging, making it difficult to detect pathological changes against a background of natural changes in cognition. Most of the tests to assess cognitive decline are artificial tasks that have little resemblance to the problems faced by people in everyday life. This means both that pe...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00074
更新日期:2015-05-18 00:00:00
abstract::Despite potential implications for the early detection of impending Alzheimer's disease (AD), very little is known about the differences of large-scale brain networks between amnestic mild cognitive impairment (aMCI) with high cerebral amyloid-beta protein (Aβ) deposition (i.e., aMCI+) and aMCI with no or very little ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00015
更新日期:2015-02-19 00:00:00
abstract::Characterizing the cognitive declines associated with aging, and differentiating them from the effects of disease in older adults, are important goals for human neuroscience researchers. This is also an issue of public health urgency in countries with rapidly aging populations. Progress toward understanding cognitive ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2012.00023
更新日期:2012-09-12 00:00:00