Abstract：
:Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, glial activation, and neurodegeneration. In mouse models, inflammatory activation of microglia accelerates tau pathology. The chemokine fractalkine serves as an endogenous neuronal modulator to quell microglial activation. Experiments with fractalkine receptor null mice suggest that fractalkine signaling diminishes tau pathology, but exacerbates amyloid pathology. Consistent with this outcome, we report here that soluble fractalkine overexpression using adeno-associated viral vectors significantly reduced tau pathology in the rTg4510 mouse model of tau deposition. Furthermore, this treatment reduced microglial activation and appeared to prevent neurodegeneration normally found in this model. However, in contrast to studies with fractalkine receptor null mice, parallel studies in an APP/PS1 model found no effect of increased fractalkine signaling on amyloid deposition. These data argue that agonism at fractalkine receptors might be an excellent target for therapeutic intervention in tauopathies, including those associated with amyloid deposition.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Nash KR,Lee DC,Hunt JB Jr,Morganti JM,Selenica ML,Moran P,Reid P,Brownlow M,Guang-Yu Yang C,Savalia M,Gemma C,Bickford PC,Gordon MN,Morgan Ddoi
10.1016/j.neurobiolaging.2012.12.011subject
Has Abstractpub_date
2013-06-01 00:00:00pages
1540-8issue
6eissn
0197-4580issn
1558-1497pii
S0197-4580(12)00642-2journal_volume
34pub_type
杂志文章abstract：:Exercise has emerged as a powerful variable that can improve cognitive function and delay age-associated cognitive decline and Alzheimer's disease (AD); however, the underlying mechanisms are poorly understood. To determine if protective mechanisms may occur at the transcriptional level, we used microarrays to investi...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.02.012
更新日期：2019-06-01 00:00:00
abstract：:Alterations in the buffering capacity of the proteostasis network are a salient feature of Alzheimer's disease, associated with the occurrence of chronic endoplasmic reticulum (ER) stress. To cope with ER stress, cells activate the unfolded protein response (UPR), a signal transduction pathway that enforces adaptive p...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/j.neurobiolaging.2017.09.012
更新日期：2018-03-01 00:00:00
abstract：:The number of Alzheimer's disease sufferers shows an alarming increase throughout the world. Therefore elucidation of the pathogenic mechanisms leading to Alzheimer's disease and the design of effective treatment, preventive or curative, became imperative. In the last few years several groups have found evidence indic...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(00)00223-2
更新日期：2000-11-01 00:00:00
abstract：:The substantia innominata (SI) contains the nucleus basalis of Meynert, which provides the major cholinergic innervation to the entire cortical mantel and the amygdala; degeneration of nucleus basalis neurons correlates with cognitive decline in Alzheimer's disease (AD). However, whether SI atrophy occurs in individua...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.11.006
更新日期：2011-10-01 00:00:00
abstract：:Hearing acuity and sound localization are affected by aging and may contribute to cognitive dementias. Although loss of sensorineural conduction is well documented to occur with age, little is known regarding short-term synaptic plasticity in central auditory nuclei. Age-related changes in synaptic transmission proper...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2018.03.015
更新日期：2018-07-01 00:00:00
abstract：:The rare variant A673T in the amyloid-β precursor protein (APP) gene has been shown to reduce the risk of cognitive impairment. We genotyped the variant in 8721 Asian individuals comprising 552 with Alzheimer's disease and vascular dementia, 790 with Parkinson's disease, and 7379 controls. The A673T variant was absent...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.04.012
更新日期：2013-10-01 00:00:00
abstract：:Four biopsies of the brain cortex of patients with Alzheimer's disease were used for ultrastructural studies. Three-dimensional reconstruction and morphometric studies of three classical plaques were carried out to determine the distribution of the astrocytes and their processes, and spatial relationships between astr...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(91)90091-w
更新日期：1991-09-01 00:00:00
abstract：:The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 123 patients with Alzheimer's disease (AD) and 57 healthy controls. Despite CSF sampling under strictly standardized conditions, a w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(92)90017-r
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVE:To determine the patterns of cerebral glucose metabolism in frontotemporal dementia (FTD) and semantic dementia (SD). METHODS:25 patients with mild FTD and 9 patients with mild SD as well as 15 healthy age-matched control subjects underwent 18F-FDG- positron emission tomography. Patient scans were compared w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.10.007
更新日期：2004-09-01 00:00:00
abstract：:The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.09.005
更新日期：2011-12-01 00:00:00
abstract：:Progranulin (PGRN) mutations account for an average of 15% of familial frontotemporal dementia (FTD) cases and 20% of total FTD cases worldwide. Here, we investigated the frequency of PGRN mutations in FTD patients (n = 116) from a clinical cohort of south India and detected one novel mutation located on exon 12 in a ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.11.026
更新日期：2016-03-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons. To date, more than 20 genes have been implicated in ALS, and of these, the 2 most frequently mutated are the superoxide dismutase 1 (SOD1) gene and the chromosome 9 open reading frame 72 (C9ORF72) gene. In t...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.01.016
更新日期：2017-05-01 00:00:00
abstract：:Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2010.09.027
更新日期：2012-02-01 00:00:00
abstract：:Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study,...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.10.023
更新日期：2012-05-01 00:00:00
abstract：:Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an importan...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.007
更新日期：2016-05-01 00:00:00
abstract：:Older adults have altered perception of the relative timing between auditory and visual stimuli, even when stimuli are scaled to equate detectability. To help understand why, this study investigated the neural correlates of audiovisual synchrony judgments in older adults using electroencephalography (EEG). Fourteen yo...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2017.03.011
更新日期：2017-07-01 00:00:00
abstract：:In the axon terminals of the locus coeruleus (LC) neurons, a high level of axonal branching was occurred in the middle-aged brain, and the increased branching was maintained in the aged brain. In the present study, we hypothesized that neurotrophic support is necessary for the morphological age-related changes seen in...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/S0197-4580(03)00093-9
更新日期：2004-03-01 00:00:00
abstract：:The genetic analysis of the yeast replicative life span has revealed the importance of metabolic control and resistance to stress. It has also illuminated the pivotal role in determining longevity that the RAS genes play by the maintenance of homeostasis. This role appears to be performed by the coordination of a vari...
journal_title：Neurobiology of aging
pub_type： 杂志文章,评审
doi：10.1016/s0197-4580(99)00095-0
更新日期：1999-09-01 00:00:00
abstract：:Accumulating evidence suggests that engagement in leisure activities is associated with favorable trajectories of cognitive aging, but little is known about brain changes related to both activities and cognition. White matter microstructure shows experience-dependent plasticity and declines in aging. Therefore, we inv...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2016.02.013
更新日期：2016-05-01 00:00:00
abstract：:Insomnia, daytime sleepiness, and nocturnal wandering, so common in the elderly, are caused largely by two specific pathophysiologic processes. Sleep apnea is a condition where respiration pauses during sleep, leading to arousal. Sleep apnea is due either to obstruction in the throat or failure of the central respirat...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(82)90021-5
更新日期：1982-01-01 00:00:00
abstract：:Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(97)80316-8
更新日期：1997-05-01 00:00:00
abstract：:Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that el...
journal_title：Neurobiology of aging
pub_type： 临床试验,杂志文章
doi：10.1016/s0197-4580(03)00032-0
更新日期：2003-11-01 00:00:00
abstract：:To study the long-term effects of prenatal diazepam (DZ) exposure, 31P NMR (nuclear magnetic resonance) spectra and levels of thiobarbituric acid (TBA)-reactive material were measured in the brains of rats from 3 to 26 months of age. In control rats, there were aging-related increases in levels of TBA-reactive materia...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(90)90044-z
更新日期：1990-03-01 00:00:00
abstract：:Clinico-pathological studies reveal that some elderly people with no cognitive impairment have high burdens of neurofibrillary tangles (NFTs), a pathology associated with Alzheimer's disease. We examined a total of 123 elderly participants without dementia and free of other neurological disorders or pathologies who at...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2015.10.012
更新日期：2016-01-01 00:00:00
abstract：:Aging increases the likelihood of cognitive decline after negative life events such as infection or injury. We have modeled this increased vulnerability in aged (24-month-old), but otherwise unimpaired F344xBN rats. In these animals, but not in younger (3-month-old) counterparts, a single intraperitoneal injection of ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.07.015
更新日期：2012-04-01 00:00:00
abstract：:The associations of 4 proteins-AK4, ITPK1, HSPB2, and IGFBP5-with cognitive function in older adults were largely unexplained by known brain pathologies. We examined the extent to which individual protein associations with cognitive decline were attributable to microstructural changes in the brain. This study included...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2019.07.013
更新日期：2019-12-01 00:00:00
abstract：:Accumulation of disease-related proteins is a characteristic event observed in the pathogenesis of neurodegenerative diseases. β-secretase (BACE)-1, which initiates generation of β-amyloid (Aβ), is increased in the Alzheimer's diseased brain. However, the mechanisms of BACE1 accumulation in Alzheimer's disease are lar...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.08.005
更新日期：2013-03-01 00:00:00
abstract：:The effects of age and estradiol on hypothalamic content and distribution of tubulin and calmodulin were examined by radioimmunoassay in ovariectomized C57BL/6J female mice. A small (14%) increase in particulate tubulin, but not soluble tubulin, was found in the hypothalamus of reproductively senescent mice (20 months...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(85)90008-9
更新日期：1985-01-01 00:00:00
abstract：:Young, middle-aged, old, and senescent Fischer 344 x Brown Norway F1 hybrid rats were trained in either the trace or delay eyeblink conditioning task in order to investigate how aging affects associative learning and memory over the life span. Senescent rats at 34-35 months showed severe impairments in acquisition of ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00194-9
更新日期：2001-01-01 00:00:00
abstract：:A circular-transcriptome-wide study has recently linked differential expression of circular RNAs (circRNAs) in brain tissue with Alzheimer's disease (AD). We aimed at replicating the major findings in an independent series of sporadic and familial AD. We also included cases with frontotemporal lobar degeneration (FTLD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.03.017
更新日期：2020-08-01 00:00:00
