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 new therapeutics for the brain. The delivery of recombinant protein or gene medicines to the brain is a binary process: either the brain drug developer re-engineers the biologic with BBB drug delivery technology, or goes forward with brain drug development in the absence of a BBB delivery platform. The presence of BBB delivery technology allows for engineering the therapeutic to enable entry into the brain across the BBB from blood. Brain drug development may still take place in the absence of BBB delivery technology, but with a reliance on approaches that have rarely led to FDA approval, e.g., CSF injection, stem cells, small molecules, and others. CSF injection of drug is the most widely practiced approach to brain delivery that bypasses the BBB. However, drug injection into the CSF results in limited drug penetration to the brain parenchyma, owing to the rapid export of CSF from the brain to blood. A CSF injection of a drug is equivalent to a slow intravenous (IV) infusion of the pharmaceutical. Given the profound effect the existence of the BBB has on brain drug development, future drug or gene development for the brain will be accelerated by future advances in BBB delivery technology in parallel with new drug discovery.
journal_name
Front Aging Neuroscijournal_title
Frontiers in aging neuroscienceauthors
Pardridge WMdoi
10.3389/fnagi.2019.00373subject
Has Abstractpub_date
2020-01-10 00:00:00pages
373issn
1663-4365journal_volume
11pub_type
杂志文章abstract::Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules....
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00426
更新日期:2018-01-04 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::A growing body of literature has demonstrated that dementia and hearing loss are interrelated. Recent interest in dementia research has expanded to brain imaging analyses with auditory function. The aim of this study was to investigate the link between hearing ability, which was assessed using pure-tone audiometry, an...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00319
更新日期:2018-10-16 00:00:00
abstract::Pure akinesia with gait freezing (PAGF) is considered a clinical phenotype of progressive supranuclear palsy. The brain atrophy and cognitive deficits in PAGF are expected to be less prominent than in classical Richardson's syndrome (RS), but this hypothesis has not been explored yet. We reviewed the medical records o...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00180
更新日期:2015-09-29 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::Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic nigrostriatal neurons, with reductions in the function and amount of dopaminergic synapses. Therefore, synapse loss and membrane-related pathology provide relevant targets for interventions in PD. We previously showed the benefic...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00057
更新日期:2017-03-20 00:00:00
abstract::Background: Gait disturbance is an early, cardinal feature of Parkinson's disease (PD) associated with falls and reduced physical activity. Progression of gait impairment in Parkinson's disease is not well characterized and a better understanding is imperative to mitigate impairment. Subtle gait impairments progress i...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.577435
更新日期:2020-10-15 00:00:00
abstract::Aging is a multifactorial phenomenon that results in several changes at cellular and molecular levels and is considered the main risk factor for some neurodegenerative diseases. Several evidence show the participation of the kallikrein-kinin system (KKS) in neurodegeneration and this system has been associated with in...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00168
更新日期:2019-07-12 00:00:00
abstract::Memory encoding and retrieval problems are inherent to aging. To date, however, the effect of aging upon the neural correlates of forming memory traces remains poorly understood. Resting-state fMRI connectivity can be used to investigate initial consolidation. We compared within and between network connectivity differ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00344
更新日期:2015-01-09 00:00:00
abstract::Microglia are dependent on signaling through the colony stimulating factor-1 receptor (CSF-1R/CD115) for growth and survival. Activation of CSF-1R can lead to cell division, while blocking CSF-1R can lead to rapid microglia cell death. CSF-1R has two ligands, the growth factors colony stimulating factor-1 (CSF-1) and ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00244
更新日期:2017-08-09 00:00:00
abstract::Aging of the central nervous system (CNS) is one of the major risk factors for the development of neurodegenerative pathologies such as Parkinson's disease (PD) and Alzheimer's disease (AD). The molecular mechanisms underlying the onset of AD and especially PD are not well understood. However, neuroinflammatory respon...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2017.00194
更新日期:2017-06-14 00:00:00
abstract::It is assumed that DNA sequences are conserved in the diverse cell types present in a multicellular organism like the human being. Thus, in order to compare the sequences in the genome of DNA from different individuals, nucleic acid is commonly isolated from a single tissue. In this regard, blood cells are widely used...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2014.00323
更新日期:2014-11-25 00:00:00
abstract::The functional neuroanatomy of finger movements has been characterized with neuroimaging in young adults. However, less is known about the aging motor system. Several studies have contrasted movement-related activity in older versus young adults, but there is inconsistency among their findings. To address this, we con...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00238
更新日期:2016-10-17 00:00:00
abstract::[This corrects the article DOI: 10.3389/fnagi.2019.00312.]. ...
journal_title:Frontiers in aging neuroscience
pub_type: 已发布勘误
doi:10.3389/fnagi.2020.00187
更新日期:2020-07-08 00:00:00
abstract::Background and Purpose: Subarachnoid hemorrhage (SAH) has long been classified into two main forms, aneurysmal SAH (aSAH) and non-aneurysmal SAH (naSAH), but the related risk factors for aSAH and naSAH are heterogeneous. Our objective was to determine the risk factors for SAH of known or unknown origin with respect to...
journal_title:Frontiers in aging neuroscience
pub_type:
doi:10.3389/fnagi.2020.573454
更新日期:2021-01-11 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::Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race. Patients/Methods: Among 1,555-1,719 Wh...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00313
更新日期:2018-10-09 00:00:00
abstract::Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reli...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00146
更新日期:2016-06-22 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::Associative processes, such as the encoding of associations between words in a list, can enhance episodic memory performance and are thought to deteriorate with age. Here, we examine the nature of age-related deficits in the encoding of associations, by using a free recall paradigm with visual arrays of objects. Fifty...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00306
更新日期:2019-11-12 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:OBJECTIVE:Early-onset Alzheimer's disease (EAD) shows distinct features from late-onset Alzheimer's disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00159
更新日期:2016-06-30 00:00:00
abstract::The enteric nervous system (ENS) poses the intrinsic innervation of the gastrointestinal tract and plays a critical role for all stages of postnatal life. There is increasing scientific and clinical interest in acquired or age-related gastrointestinal dysfunctions that can be manifested in diseases such as gut constip...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00276
更新日期:2014-10-15 00:00:00
abstract::It is common wisdom that practice makes perfect; but why do some adults learn better than others? Here, we investigate individuals' cognitive and social profiles to test which variables account for variability in learning ability across the lifespan. In particular, we focused on visual learning using tasks that test t...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00105
更新日期:2015-06-10 00:00:00
abstract::Objective: To study the dynamics of clustering semantic fluency responses and switching between clusters. Methods: We conducted a cross-sectional study of participants (N = 60) in a study of patient reported outcomes who were given the Saint Louis University Mental Status test. Sixty-second animal naming tests were sc...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00252
更新日期:2016-10-25 00:00:00
abstract::Recent studies have shown that Liuwei Dihuang pills (LWPs) can positively affect learning, memory and neurogenesis. However, the underlying molecular mechanisms are not understood. In the present study, we developed ALWPs, a mixture of Antler and LWPs, and investigated whether ALWPs can affect neuroinflammatory respon...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00269
更新日期:2018-09-26 00:00:00
abstract::While functioning in multiple domains declines with age, emotional regulation appears to remain preserved in older adults. The Emotion Inhibition (Emotional Stroop) Test requires participants to name the ink color in which neutrally and emotionally valenced words are printed. It was employed in the current investigati...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2010.00141
更新日期:2010-09-30 00:00:00
abstract::Inter-temporal choice depends on multiple, interacting systems, some of which may be compromised with age. Some of these systems may be responsible for ongoing trial-by-trial choice strategies. Some may represent the consequences of action. Some may be necessary for the coupling between anticipated consequences and st...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00041
更新日期:2015-03-27 00:00:00
abstract::Deep learning, a state-of-the-art machine learning approach, has shown outstanding performance over traditional machine learning in identifying intricate structures in complex high-dimensional data, especially in the domain of computer vision. The application of deep learning to early detection and automated classific...
journal_title:Frontiers in aging neuroscience
pub_type:
doi:10.3389/fnagi.2019.00220
更新日期:2019-08-20 00:00:00
abstract::Cognitive Reserve is the capital of knowledge and experiences that an individual acquires over their life-span. Cognitive Reserve is strictly related to Brain Reserve, which is the ability of the brain to cope with damage. These two concepts could explain many phenomena such as the modality of onset in dementia or the...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00429
更新日期:2017-12-22 00:00:00