Abstract:
:Alzheimer's disease (AD) is a late-onset and progressive neurodegenerative disorder characterized clinically by memory loss, impairment of other cognitive functions, and changes in behavior and personality. The overall aim of this review is to summarize recent advances in studies of AD progression and the use of animal models in gene expression studies of AD progression. Genetic causes of AD are known only for early-onset AD patients. For a majority of late-onset AD patients, causal factors are still unknown. Currently, there are no early detectable biomarkers for late-onset AD, and there is a lack of understanding of AD pathophysiology, particularly at the early stages of disease progression, before pathology develops. Human histopathological and biochemical studies provide valuable information regarding the last stages of AD pathogenesis. However, to understand early cellular changes in AD progression before symptoms develop, animal models are still our only alternative. Several research groups have created genetically engineered animal models, particularly models of the mouse, rat, fly, and worm, which have allowed us to better, understand the initiating events of AD progression. Recently, state-of-the-art methods have helped elucidate gene expression changes in affected and unaffected tissues from postmortem AD brains and from animal models developed for AD studies. These methods allow the investigation of mRNA-based transcriptosomal profiles of brain specimens from AD humans and transgenic animals. The major finding from these studies is that AD progression and pathogenesis involve multiple cellular pathways, which suggests that AD is a complex and heterogeneous disease.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Reddy PH,McWeeney Sdoi
10.1016/j.neurobiolaging.2005.04.014subject
Has Abstractpub_date
2006-08-01 00:00:00pages
1060-77issue
8eissn
0197-4580issn
1558-1497pii
S0197-4580(05)00196-Xjournal_volume
27pub_type
杂志文章,评审abstract::Glycogen synthase kinase-3β (GSK3B) and cyclin-dependent kinase 5 (CDK5) are the 2 major protein kinases involved in abnormal phosphorylation of tau. To determine their potential role in the pathogenesis of Parkinson's disease (PD) we analyzed 2 functional single nucleotide polymorphisms (SNPs) of GSK3B (rs334558 and ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2010.10.016
更新日期:2012-07-01 00:00:00
abstract::We conducted genetic analysis of the fused in sarcoma gene (FUS) in Chinese Han patients with essential tremor (ET) in a case-control association study. One hundred eighty unrelated patients with ET were screened for mutations in the coding region and exon-intron boundaries of FUS. Reverse transcriptase polymerase cha...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.03.001
更新日期:2013-08-01 00:00:00
abstract::We identified and validated several novel inflammatory markers of cognitive performance in community-living older persons. An exploratory study (n = 83) correlated 177 inflammatory markers assayed by Luminex with the Mini-Mental State Examination (MMSE) and identified 8 inflammatory markers for enzyme-linked immunosor...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.12.002
更新日期:2016-03-01 00:00:00
abstract::Since diabetes is a risk factor for Alzheimer's disease (AD), we asked if there is a functional interaction between high glucose and elevated beta amyloid peptide (Abeta) in cultured brain microvascular endothelial cells and presymptomatic AD transgenic mice. When cultured brain microvascular endothelial cells are exp...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2008.02.010
更新日期:2009-12-01 00:00:00
abstract::Tyrosine hydroxylase (TH) mRNA, immunoreactivity, and activity were examined as a reflection of dopamine expression in juxtaglomerular neurons intrinsic to the olfactory bulbs of young (6-month-old), middle aged (18-month-old), and aged (25- to 29-month-old) rats and mice. TH expression was maintained at levels observ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(94)00152-9
更新日期:1995-03-01 00:00:00
abstract::The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, an...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2005.03.021
更新日期:2006-05-01 00:00:00
abstract::The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the oth...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(95)02074-8
更新日期:1996-03-01 00:00:00
abstract::Type 2 diabetes mellitus is a risk factor of Alzheimer's disease (AD), most likely linked to an impairment of insulin signaling in the brain. Liraglutide, a novel long-lasting glucagon-like peptide 1 (GLP-1) analog, facilitates insulin signaling and shows neuroprotective properties. In the present study, we analyzed t...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.04.009
更新日期:2013-02-01 00:00:00
abstract::The 'amyloid hypothesis' has guided research into Alzheimer's disease (AD) for more than a decade. A detailed review of the relevant data led us to conclude that some data, particularly those from transgenic mice, are inconsistent with the predictions of the amyloid hypothesis. Instead, most data are consistent with t...
journal_title:Neurobiology of aging
pub_type: 评论,杂志文章,评审
doi:10.1016/s0197-4580(02)00050-7
更新日期:2002-11-01 00:00:00
abstract::We investigated whether (1) serum levels of 25-hydroxyvitamin D [25(OH)D] and single nucleotide polymorphisms (SNPs) in the group-specific component (GC) gene-regulating serum 25(OH)D levels are associated with cognition in older individuals; and (2) whether causal relationships exist between 25(OH)D and cognition dur...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2015.11.002
更新日期:2016-03-01 00:00:00
abstract::Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding var...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2019.02.001
更新日期:2019-06-01 00:00:00
abstract::Age at the time of brain injury is generally considered an important determinant in recovery of function. The implication is that older individuals show less recovery. Existing data challenge this common notion, but suggest differential effects of brain damage in aged subjects. To assess these differences old rats wer...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(83)90018-0
更新日期:1983-10-01 00:00:00
abstract::Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease that resembles early-onset frontotemporal dementia with bone lesions called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with Alzheimer's...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2017.12.008
更新日期:2018-04-01 00:00:00
abstract::Studies in asymptomatic granulin gene (GRN) mutation carriers are essential to improve our understanding of the pattern and timing of early morphologic brain changes in frontotemporal lobar degeneration. The main objectives of this study were to assess the effect of age in cortical thickness changes (CTh) in preclinic...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.11.005
更新日期:2013-05-01 00:00:00
abstract::A loss of hippocampal neurons and synapses had been considered a hallmark of normal aging and, furthermore, to be a substrate of age-related learning and memory deficits. Recent stereological studies in humans have shown that only a relatively minor neuron loss occurs with aging and that this loss is restricted to spe...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(98)00098-0
更新日期:1998-11-01 00:00:00
abstract::Although peripheral nerves are capable of regeneration, advanced age decreases the potential for functional recovery after injury. The cellular mechanisms for this are not currently understood. Here, we performed sciatic nerve grafting with young (2 months old) and aged (18 months old) Brown-Norway male rats, in which...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2016.05.004
更新日期:2016-09-01 00:00:00
abstract::In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkin...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.05.026
更新日期:2018-09-01 00:00:00
abstract::This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, ...
journal_title:Neurobiology of aging
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.neurobiolaging.2018.05.033
更新日期:2018-10-01 00:00:00
abstract::The abnormal proliferation and neurogenesis of neural progenitor cells (NPCs) is usually associated with the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). Mitochondrial stress is one of the most prominent features of AD and is thought to be involved in the impairment of the neurogene...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2019.05.002
更新日期:2019-08-01 00:00:00
abstract::Sex differences in cerebral white matter (WM) aging have been debated extensively over the past 2 decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on WM microstructure differ between sexes. Artery elasticity via carotid artery compliance (CAC) and WM diffusion ...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2018.02.012
更新日期:2018-06-01 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::N-Methyl-D-Aspartate (NMDA) receptors are believed to play a critical role in excitotoxic cell death in the CNS. The distribution of NMDA-preferring binding sites is compared here with the patterns of selective neuronal death observed in Alzheimer's disease and following transient ischemia. The distribution of NMDA re...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/0197-4580(89)90148-6
更新日期:1989-09-01 00:00:00
abstract::We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Ba...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2013.03.025
更新日期:2013-10-01 00:00:00
abstract::Few studies have examined gender differences in hippocampal volumes, and the potential effect of estrogen on these measures has not been well studied. We used MRI to measure hippocampal volumes in elderly Mexican American men and women subjects in order to determine if there were gender differences and if estrogen rep...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/s0197-4580(02)00056-8
更新日期:2003-09-01 00:00:00
abstract::We present a fresh approach to evaluating association with candidate genes and cognitive change by testing association for parameters describing individual growth curves from twins. Moderate genetic influences on memory in aging adults has been shown in quantitative genetic studies. A recently reported, association of...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2004.12.009
更新日期:2006-01-01 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::Accumulating evidence indicates that white matter degeneration contributes to the neural disconnections that underlie Alzheimer's disease pathophysiology. Although this white matter degeneration is partly attributable to axonopathy associated with neuronal degeneration, amyloid β (Aβ) protein-mediated damage to oligod...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2010.05.007
更新日期:2012-03-01 00:00:00
abstract::Several polymorphisms in hepatic lipase (LIPC) are similar to apoE4 because they associate with cholesterol concentrations and, for rs6084, coronary artery disease (CAD). Since apoE4 is also a primary genetic risk factor for late-onset Alzheimer's disease (LOAD), LIPC single nucleotide polymorphisms (SNP)s represent e...
journal_title:Neurobiology of aging
pub_type: 杂志文章,多中心研究
doi:10.1016/j.neurobiolaging.2006.11.015
更新日期:2008-05-01 00:00:00
abstract::Patients with Mild Cognitive Impairment (MCI), exhibiting both working memory and olfactory deficits are likely to progress to Alzheimer's disease (AD). Targeting this pre-clinical AD population with disease modifying agents or cognitive enhancers represents the best strategy for halting or delaying the impact of this...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2007.11.018
更新日期:2009-09-01 00:00:00
abstract::Neuronal inclusions of α-synuclein (α-syn), termed Lewy bodies, are a hallmark of Parkinson disease (PD). Increased α-syn levels can occur in brains of aging human and neurotoxin-treated mice. Because previous studies have shown increased brain lactate levels in aging brains, in PD affected subjects when compared with...
journal_title:Neurobiology of aging
pub_type: 杂志文章
doi:10.1016/j.neurobiolaging.2012.11.001
更新日期:2013-05-01 00:00:00