Abstract：
:Mitochondrial dysfunction is likely a significant contributing factor to Alzheimer disease pathogenesis, and both amyloid peptide (Aβ) and pathological forms of tau may contribute to this impairment. Cleavage of tau at Asp421 occurs early in Alzheimer disease, and Asp421-cleaved tau likely negatively impacts neuronal function. Previously we showed that expression of Asp421-cleaved tau in a neuronal cell model resulted in mitochondrial impairment. To extend these findings we expressed either full length tau or Asp421-cleaved tau (truncated tau) in primary cortical neurons and measured different aspects of mitochondrial function with or without the addition of sublethal concentrations of Aβ. The expression of truncated tau alone induced significant mitochondrial fragmentation in neurons. When truncated tau expression was combined with Aβ at sublethal concentrations, increases in the stationary mitochondrial population and the levels of oxidative stress in cortical neurons were observed. Truncated tau expression also enhanced Aβ-induced mitochondrial potential loss in primary neurons. These new findings show that Asp421-cleaved tau and Aβ cooperate to impair mitochondria, which likely contributes to the neuronal dysfunction in Alzheimer disease.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Quintanilla RA,Dolan PJ,Jin YN,Johnson GVdoi
10.1016/j.neurobiolaging.2011.02.007subject
Has Abstractpub_date
2012-03-01 00:00:00pages
619.e25-35issue
3eissn
0197-4580issn
1558-1497pii
S0197-4580(11)00020-0journal_volume
33pub_type
杂志文章abstract：:While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60+/-10 years, range 36-86) were examined to determine the relation...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.08.019
更新日期：2009-05-01 00:00:00
abstract：:Regions of diffuse periventricular white matter hyperintensities (PVWMH) are a common finding on T(2)-weighted MRI scans of older subjects, but their aetiology remains unclear. The aim of this study was to characterize differences in water diffusion and magnetization transfer MRI parameters between macroscopically nor...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2007.05.013
更新日期：2009-01-01 00:00:00
abstract：:Although neuroactive steroids exert neuroprotective actions in different experimental models of neurodegenerative diseases, including those of Alzheimer's disease (AD), their relationships with aged related physiologic and pathologic brain changes remain to be clarified. In this study the levels of pregnenolone, dehyd...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.10.007
更新日期：2013-04-01 00:00:00
abstract：:Aged rats perform poorly on spatial learning tasks, a cognitive impairment which has been linked to the failure of hippocampal networks to fully encode changes in the external environment [Barnes CA, Suster MS, Shen J, McNaughton BL. Multistability of cognitive maps in the hippocampus of old rats. Nature 1997;388(6639...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2004.09.006
更新日期：2005-07-01 00:00:00
abstract：:Alzheimer's disease (AD) is a genetically complex disorder for which the definite diagnosis is only accomplished postmortem. Mutations in 3 genes (APP, PSEN1, and PSEN2) are known to cause AD, but a large number of familial cases do not harbor mutations in these genes and several unidentified genes that contain diseas...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2011.10.009
更新日期：2012-05-01 00:00:00
abstract：:The G4C2 hexanucleotide repeat expansion, located in the first intron of the C9ORF72 gene, represents a major genetic hallmark of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Several hypotheses have been proposed on how the transcribed repeat RNA leads to the development of amyotrophic lateral ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.09.012
更新日期：2015-02-01 00:00:00
abstract：:The reaction of lysine and arginine residues of proteins with 1,2-dicarbonyl compounds result in the formation of advanced glycation end products (AGEs). Accumulation of AGEs is a characteristic feature of the aging brain and contributes to the development of neurodegenerative diseases such as Alzheimer's disease (AD)...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2005.11.007
更新日期：2007-01-01 00:00:00
abstract：:The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and memory and increased amyloid beta (Aβ) peptide accumulation at 12 months. To detect differences in gene expression in SAMP8 mice, we used a control mouse that was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.07.018
更新日期：2014-01-01 00:00:00
abstract：:Cerebral small vessel disease (SVD) and inflammation are increasingly recognized as key contributors to Alzheimer's disease (AD), although the timing, trajectory, and relation between them early in the disease process is unclear. Therefore, to investigate very early-stage changes, we compared 158 healthy midlife adult...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.10.029
更新日期：2020-11-02 00:00:00
abstract：:Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We invest...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.07.005
更新日期：2015-01-01 00:00:00
abstract：:The sporadic form of Alzheimer disease, late onset Alzheimer's disease (LOAD), is a multifactorial disease; a strong link between nutritional and genetic factors with normal aging and dementia is supported by studies on nutrition, metabolism, and neurodegeneration. Specifically, the involvement of homocysteine (HCY) a...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/j.neurobiolaging.2011.01.012
更新日期：2011-07-01 00:00:00
abstract：:Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: 3 months after surgery, excitotoxic lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of aged rats relative to young adults. To determine whether the differential...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2003.08.003
更新日期：2004-08-01 00:00:00
abstract：:Patients with posterior cortical atrophy (PCA-AD) show more severe visuospatial and perceptual deficits than those with typical AD (tAD). The aim of this study was to investigate whether functional alterations measured by electroencephalography can help understand the mechanisms that explain this clinical heterogeneit...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.07.029
更新日期：2020-12-01 00:00:00
abstract：:Aging produces a loss in a number of behavioral and cognitive functions, including sleep. Hypocaloric diet is one of the few methods that have been shown to retard the effects due to age. However, the effects of such a diet on sleep have never been investigated. In the present study, 21 months old male F344 rats fed a...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(02)00030-1
更新日期：2002-09-01 00:00:00
abstract：:Aged rats were chronically administered acetyl-L-carnitine (AC) for 10 months. During this period they were tested on learning and sensorimotor tasks and were then subsequently tested electrophysiologically to assess induction and decay rates of long-term synaptic enhancement (LTE) in the hippocampus. Four groups were...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(93)90030-f
更新日期：1993-01-01 00:00:00
abstract：:In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(95)97327-d
更新日期：1995-05-01 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a complex fatal neurodegenerative disease characterized by progressive degeneration and loss of upper motor neurons in the cerebral cortex and lower motor neurons in brainstem and spinal cord. We established the frequencies of mutations in 4 major ALS-associated genes, SOD1, TARD...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.11.011
更新日期：2015-03-01 00:00:00
abstract：:Heparan sulfate proteoglycans (HSPGs) are ubiquitously present within the perivascular basement membrane, and have been shown to be altered in patients with Alzheimer's Disease (AD). Although the HSPG agrin clearly orchestrates the differentiation of the neuromuscular junction, its role in the brain remains unclear. G...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(00)00121-4
更新日期：2000-03-01 00:00:00
abstract：:The development of amyloid imaging compounds has allowed in vivo imaging of amyloid deposition. In this study, we examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue ((11)C-PiB) positron emission tomography data from the Baltimore Longitudinal Study of Aging. We used...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2013.05.030
更新日期：2013-12-01 00:00:00
abstract：:White matter hyperintensities (WMH) are generally considered to be associated with cerebral small vessel disease, especially, in older age. Although significant sex differences have been reported in the severity of WMH, it is not yet known if the risk factors for WMH differ in men and women. In this study, magnetic re...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2020.11.001
更新日期：2020-11-10 00:00:00
abstract：:Parkinson's disease (PD) and Alzheimer's dementia (AD) are often associated with an autonomic neuropathy. The extent of autonomic involvement, however is poorly defined and unpredictable. In order to assess the autonomic cardiovascular regulation baroreflex sensitivity (BRS) was determined non-invasively in 23 patient...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/s0197-4580(01)00210-x
更新日期：2001-05-01 00:00:00
abstract：:An age-related phosphorylation of the 200kD neurofilament protein (NF200) has been observed in the axons of cerebellar basket cells of normal human fixed brain tissue from individuals older than 60 years, but not in younger individuals. The probe for this study was the monoclonal antibody SMI-34 which detects a phosph...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90059-6
更新日期：1989-05-01 00:00:00
abstract：:RACK1 (receptor for activated C-kinase 1), an anchoring protein that shuttles activated PKC to cellular membranes, plays an important role in PKC-mediated signal transduction pathways. A significant loss of RACK1 has been found in the brain of aging animals and Alzheimer's disease (AD) patients, which implicates the p...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.10.017
更新日期：2011-10-01 00:00:00
abstract：:We examined the interaction of brain atrophy and white matter lesions (WML) with cognitive functioning in 605 patients (mean age, 58±10; 76% men) with atherosclerotic disease from the Second Manifestations of ARTerial disease-MR substudy (SMART-MR study). Automated brain segmentation was used to quantify volumes of br...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2009.05.005
更新日期：2011-05-01 00:00:00
abstract：:Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (Neur...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2014.07.038
更新日期：2015-01-01 00:00:00
abstract：:Data are emerging that the altered development of adrenocortical and emotional reactivity in individuals exposed perinatally to adverse events is reflected in cognitive change and that maternal care is an important determinant. However, early trauma does not cause a generalized cognitive decline at older age, but rath...
journal_title：Neurobiology of aging
pub_type： 评论,杂志文章,评审
doi：10.1016/s0197-4580(03)00057-5
更新日期：2003-05-01 00:00:00
abstract：:Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(96)00062-0
更新日期：1996-07-01 00:00:00
abstract：:Using resting state (RS) functional magnetic resonance imaging and independent component analysis, the integrity of brain networks related to cognition and behavior was investigated in 20 nondemented patients with amyotrophic lateral sclerosis (ALS). The association between RS functional connectivity and executive fun...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/j.neurobiolaging.2012.04.015
更新日期：2013-02-01 00:00:00
abstract：:We designed this study to determine whether the sexual behavior of male monkeys changes on a diurnal schedule that coincides with changes in the levels of hormones such as luteinizing hormone (LH), testosterone, estradiol, and cortisol, and whether these differences vary with age. Old (n = 8) and young (n = 8) males w...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(82)90059-8
更新日期：1982-04-01 00:00:00
abstract：:Recent results support the hypothesis that microglia and/or macrophages of the brain, by producing oxidants, could play a role in the local inactivation of the Kunitz protease inhibitor (KPI) domain of beta-amyloid precursor protein (APP), thereby facilitating deposition of abnormal amyloid filaments in patients with ...
journal_title：Neurobiology of aging
pub_type： 杂志文章
doi：10.1016/0197-4580(89)90099-7
更新日期：1989-09-01 00:00:00
