Abstract:
:The focus on amyloid plaques and neurofibrillary tangles has yielded no Alzheimer's disease (AD) modifying treatments in the past several decades, despite successful studies in preclinical mouse models. This inconsistency has caused a renewed focus on improving the fidelity and reliability of AD mouse models, with disparate views on how this improvement can be accomplished. However, the interactive effects of the universal biological variables of AD, which include age, APOE genotype, and sex, are often overlooked. Age is the greatest risk factor for AD, while the ε4 allele of the human APOE gene, encoding apolipoprotein E, is the greatest genetic risk factor. Sex is the final universal biological variable of AD, as females develop AD at almost twice the rate of males and, importantly, female sex exacerbates the effects of APOE4 on AD risk and rate of cognitive decline. Therefore, this review evaluates the importance of context for understanding the role of APOE in preclinical mouse models. Specifically, we detail how human AD pathology is mirrored in current transgenic mouse models ("What") and describe the critical need for introducing human APOE into these mouse models ("Who"). We next outline different methods for introducing human APOE into mice ("How") and highlight efforts to develop temporally defined and location-specific human apoE expression models ("When" and "Where"). We conclude with the importance of choosing the human APOE mouse model relevant to the question being addressed, using the selection of transgenic models for testing apoE-targeted therapeutics as an example ("Why").
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Lewandowski CT,Maldonado Weng J,LaDu MJdoi
10.1016/j.nbd.2020.104811subject
Has Abstractpub_date
2020-06-01 00:00:00pages
104811eissn
0969-9961issn
1095-953Xpii
S0969-9961(20)30086-3journal_volume
139pub_type
杂志文章,评审abstract:OBJECTIVE:In Parkinson's disease, chronic striatal dopamine depletion results in over-activity and under-activity of the indirect and direct striatal output pathways respectively. In this study, we investigated changes in the function of glutamatergic cortico-striatal synapses that contribute to abnormalities in striat...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.10.013
更新日期:2011-03-01 00:00:00
abstract::Patients with Krabbe disease, a genetic demyelinating syndrome caused by deficiency of galactosyl-ceramidase and the resulting accumulation of galactosyl-sphingolipids, develop signs of a dying-back axonopathy compounded by a deficiency of large-caliber axons. Here, we show that axonal caliber in Twitcher mice, an ani...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.01.013
更新日期:2012-05-01 00:00:00
abstract::Deep brain stimulation for epilepsy has garnered attention from epileptologists due to its well-documented success in treating movement disorders and the low morbidity associated with the implantation of electrodes. Given the large proportion of patients who fail medical therapy and are not candidates for surgical ame...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.07.007
更新日期:2010-06-01 00:00:00
abstract::Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104627
更新日期:2020-02-01 00:00:00
abstract::Malfunction of the ubiquitin-proteasome system has been implicated as a causal factor in the pathogenesis of aggregation-related disorders, e.g. Parkinson's disease. We show here that Transforming growth factor-beta 1 (TGF-beta), a multifunctional cytokine and trophic factor for dopaminergic (DAergic) neurons modulate...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.02.011
更新日期:2010-06-01 00:00:00
abstract::Chronic microglial activation has been linked to the progressive degeneration of the nigrostriatal dopaminergic neurons evidenced in Parkinson's disease (PD) pathogenesis. The exact etiology of PD remains poorly understood. Although both oxidative stress and neuroinflammation are identified as co-contributors in PD pa...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2016.04.008
更新日期:2016-09-01 00:00:00
abstract::Axonal damage, a core feature of neurological diseases, induces a retrograde reaction in neurons and surrounding glia. We determined transcriptional profiles of this reaction using Affymetrix oligonucleotide arrays. Gene expression was examined in spinal cord tissue prior to injury and following ventral root avulsion ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.05.016
更新日期:2006-10-01 00:00:00
abstract::Copper is an essential trace metal which plays a fundamental role in the biochemistry of the human nervous system. Menkes disease and Wilson disease are inherited disorders of copper metabolism and the dramatic neurodegenerative phenotypes of these two diseases underscore the essential nature of copper in nervous syst...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.1999.0250
更新日期:1999-08-01 00:00:00
abstract::Since aberrant miRNA expression has been implicated in numerous brain diseases, we studied miRNA expression and miRNA regulation of important signaling pathways during temporal lobe epileptogenesis in order to identify possible targets for epilepsy therapy. The temporal profile of miRNA expression was analyzed in thre...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.10.026
更新日期:2014-02-01 00:00:00
abstract::A crucial question in polyQ-induced neurodegeneration is the influence of wild type protein on the formation of aggregates and toxicity. Recently it was shown that non-expanded ataxin-3 protein mitigated neurodegeneration in a Drosophila and mouse model of SCA3. We now explored the effects of overexpressing non-expand...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.01.005
更新日期:2010-04-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are involved in tissue repair, cell death and morphogenesis. We investigated the role of the gelatinases MMP-2 and MMP-9 in the pathogenesis of neuronal death induced by prolonged seizures in the developing brain. Seven-day-old rats, MMP-9 knockout mice and transgenic rats overexpressi...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.06.023
更新日期:2012-12-01 00:00:00
abstract::It is widely accepted that the angiotensin AT2-receptor (AT2R) has neuroprotective features. In the present study we tested pharmacological AT2R-stimulation as a therapeutic approach in a model of spinal cord compression injury (SCI) in mice using the novel non-peptide AT2R-agonist, Compound 21 (C21). Complementary ex...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.11.008
更新日期:2013-03-01 00:00:00
abstract::The critical anabolic and trophic role of signaling by insulin-like growth factors (IGF) I and II via the type-I IGF receptor (IGF-IR) is reviewed throughout the life of skeletal myocytes. The proliferative effects of IGF-IR stimulation, both during embryogenesis and during satellite cell proliferation following dener...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1006/nbdi.2001.0416
更新日期:2001-08-01 00:00:00
abstract::Frontotemporal dementia (FTD) is the second most common type of primary degenerative dementia. Some patients present an overlap between Alzheimer's disease (AD) and FTD both in neuropathological and clinical aspects. This may suggest a similar overlap in physiopathology, namely an involvement of mitochondrial DNA (mtD...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.11.004
更新日期:2004-03-01 00:00:00
abstract::Twelve- to sixteen-month-old (G2019S) LRRK2 transgenic mice prepared by us displayed progressive neuronal death of substantia nigra pars compacta (SNpc) dopaminergic cells. In the present study, we hypothesized that prior to a late-phase death of SNpc dopaminergic neurons, (G2019S) LRRK2 also causes an early-phase neu...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.04.021
更新日期:2014-08-01 00:00:00
abstract::The aim of the present study is to better understand oxygen-sensitive adaptative pathways underlying the hypoxic preconditioning-induced protection of the brain against ischemia. Using oligonucleotide microarrays, we examined the brain genomic response of adult mice following hypoxia preconditioning (8% O2 for 1 or 6 ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.06.002
更新日期:2006-01-01 00:00:00
abstract::Charcot-Marie-Tooth disease (CMT) is a genetic disorder that can be caused by aberrations in >80 genes. CMT has heterogeneous modes of inheritance, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive. Over 95% of cases are dominantly inherited. In this study, we investigated wh...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.01.006
更新日期:2017-04-01 00:00:00
abstract::beta-Amyloid is cytotoxic to neurons in culture by increasing hydrogen peroxide and altering calcium homeostasis. We have evaluated the cytotoxicty of beta-amyloid peptides (betaA(25-35) and betaA(1-40)) and generation of hydrogen peroxide on cortical cultured astrocytes. Twenty-four hours after a single addition of e...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2000.0313
更新日期:2000-08-01 00:00:00
abstract::We determined whether the preferential toxicity of tetrahydrobiopterin (BH4) on dopamine-producing cells, which we have previously observed in vitro, might also occur in vivo and generate characteristics associated with Parkinson's disease. Intrastriatal BH4 injection caused a loss of tyrosine hydroxylase immunoreacti...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/s0969-9961(03)00037-8
更新日期:2003-07-01 00:00:00
abstract::Familial amyotrophic lateral sclerosis (FALS) has been modeled in transgenic mice by introducing mutated versions of human genomic DNA encompassing the entire gene for Cu,Zn superoxide dismutase (SOD1). In this setting, the transgene is expressed throughout the body and results in mice that faithfully recapitulate man...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.06.005
更新日期:2005-12-01 00:00:00
abstract::Dravet syndrome is a severe infantile-onset epileptic encephalopathy which begins with febrile seizures and is caused by heterozygous loss-of-function mutations of the voltage-gated sodium channel gene SCN1A. We designed a CRISPR-based gene therapy for Scn1a-haplodeficient mice using multiple guide RNAs (gRNAs) in the...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.104954
更新日期:2020-07-01 00:00:00
abstract::The interplay between excitatory and inhibitory circuits underlies the brain's processes and their dysregulation has been linked to cognitive decline, psychiatric disorders and epilepsy. In patients with Alzheimer's disease (AD), an elevated occurrence of seizures has been observed in both sporadic and familial forms ...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2019.04.010
更新日期:2019-07-01 00:00:00
abstract::Thermal hyperpnea, a pattern of breathing during hyperthermia that is characterized by an increase in tidal volume as well as breathing frequency, is known to lead to respiratory alkalosis. Thermal hyperpnea-induced respiratory alkalosis is linked to febrile seizures (FS). The heat-sensitive transient receptor potenti...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.08.004
更新日期:2018-11-01 00:00:00
abstract::Intermittent hypoxia (IH) during sleep induces temporally defined increases in apoptosis within vulnerable brain regions such as the hippocampal CA1 region in rats. Protein kinase B (AKT) has emerged as major signal transduction protein underlying inhibition of apoptosis and consequent increases in cell survival. Spra...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2003.08.004
更新日期:2003-12-01 00:00:00
abstract::Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased gli...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.032
更新日期:2012-08-01 00:00:00
abstract::Immunization of mouse models of Alzheimer disease (AD) with amyloid-peptide (Abeta) reduces Abeta deposits and attenuates their memory and learning deficits. Recent clinical trials were halted due to meningoencephalitis, presumably induced by T cell mediated and/or Fc-mediated immune responses. Because injection of an...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.04.012
更新日期:2006-09-01 00:00:00
abstract::Toll-like receptors (TLRs) are mediators of the innate immune response to exogenous pathogens. They have also been implicated in sterile inflammation associated with systemic injury and non-infectious diseases via binding of endogenous ligands, possibly released by damaged cells. Emerging evidence indicates that some ...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.12.012
更新日期:2013-06-01 00:00:00
abstract::Frontotemporal dementia (FTD) is one of the most prevalent forms of early-onset dementia. It represents part of the FTD-Amyotrophic Lateral Sclerosis (ALS) spectrum, a continuum of genetically and pathologically overlapping disorders. FTD-causing mutations in CHMP2B, a gene encoding a core component of the heteromeric...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2020.105047
更新日期:2020-10-01 00:00:00
abstract::Lyme disease, caused by the bacterium Borrelia burgdorferi, can cause multi-systemic signs and symptoms, including peripheral and central nervous system disease. This review examines the evidence for and mechanisms of inflammation in neurologic Lyme disease, with a specific focus on the central nervous system, drawing...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2009.11.016
更新日期:2010-03-01 00:00:00
abstract::Astrocytes are abundant neuron-supporting glial cells that harbor a powerful arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here we examined whether enrichment with healthy striatal astrocytes can provide neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A (5-...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.08.003
更新日期:2013-11-01 00:00:00