Automated differentiation of pre-diagnosis Huntington's disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: the IMAGE-HD study.

Abstract:

:We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pre-HD individuals from controls and we utilised feature selection and dimension reduction to increase the robustness of the discrimination method. Thirty six symptomatic HD (symp-HD), 35 pre-HD, and 36 control individuals participated as part of the IMAGE-HD study and underwent T1-weighted MRI, and DTI using a Siemens 3 Tesla scanner. Volume and DTI measures [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for each group within five regions of interest (ROI; caudate, putamen, pallidum, accumbens and thalamus). QDA was then performed in a stepwise manner to differentiate pre-HD individuals from controls, based initially on unimodal analysis of motor or neurocognitive measures, or on volume, MD or FA measures from within the caudate, pallidum and putamen. We then tested for potential improvements to this model, by examining multi-modal MRI classifications (volume, FA and MD), and also included motor and neurocognitive measures, and additional brain regions (i.e., accumbens and thalamus). Volume, MD and FA differed across the three groups, with pre-HD characterised by significant volumetric reductions and increased FA within caudate, putamen and pallidum, relative to controls. The QDA results demonstrated that the differentiation of pre-HD from controls was highly accurate when both volumetric and diffusion data sets from basal ganglia (BG) regions were used. The highest discriminative accuracy however was achieved in a multi-modality approach and when including all available measures: motor and neurocognitive scores and multi-modal MRI measures from the BG, accumbens and thalamus. Our QDA findings provide evidence that combined multi-modal imaging measures can accurately classify individuals up to 15 years prior to onset when therapeutic intervention is likely to have maximal effects in slowing the trajectory of disease development.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Georgiou-Karistianis N,Gray MA,Domínguez D JF,Dymowski AR,Bohanna I,Johnston LA,Churchyard A,Chua P,Stout JC,Egan GF

doi

10.1016/j.nbd.2012.10.001

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

82-92

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(12)00329-4

journal_volume

51

pub_type

杂志文章
  • Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE epsilon4 allele, in relation to cognitive function and cerebral glucose metabolism.

    abstract::Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying epsilon4 allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity a...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2006.07.013

    authors: Darreh-Shori T,Brimijoin S,Kadir A,Almkvist O,Nordberg A

    更新日期:2006-11-01 00:00:00

  • Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation.

    abstract::The use of energy substrates, such as lactate and pyruvate, has been shown to improve synaptic function when administered during glucose deprivation. In the present study, we investigated whether prolonged incubation with monocarboxylate (pyruvate or lactate) prior rather than during glucose deprivation can also susta...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2011.08.002

    authors: Shetty PK,Sadgrove MP,Galeffi F,Turner DA

    更新日期:2012-01-01 00:00:00

  • Proapoptotic effects of tau cleavage product generated by caspase-3.

    abstract::Using an in vitro translation assay to screen a human brain cDNA library, we isolated the microtubule-associated protein Tau and determined it to be a caspase-3 substrate whose C-terminal cleavage occurred during neuronal apoptosis. DeltaTau, the 50-kDa cleavage product, was detected by Western blot in apoptotic corti...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.2000.0335

    authors: Chung CW,Song YH,Kim IK,Yoon WJ,Ryu BR,Jo DG,Woo HN,Kwon YK,Kim HH,Gwag BJ,Mook-Jung IH,Jung YK

    更新日期:2001-02-01 00:00:00

  • Delayed administration of high dose human immunoglobulin G enhances recovery after traumatic cervical spinal cord injury by modulation of neuroinflammation and protection of the blood spinal cord barrier.

    abstract:BACKGROUND/INTRODUCTION:The neuroinflammatory response plays a major role in the secondary injury cascade after traumatic spinal cord injury (SCI). To date, systemic anti-inflammatory medications such as methylprednisolone sodium succinate (MPSS) have shown promise in SCI. However, systemic immunosuppression can have d...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2020.105187

    authors: Chio JCT,Wang J,Surendran V,Li L,Zavvarian MM,Pieczonka K,Fehlings MG

    更新日期:2021-01-01 00:00:00

  • Transgenic mice over-expressing GABA(B)R1a receptors acquire an atypical absence epilepsy-like phenotype.

    abstract::In this study, we tested whether over-expressing the GABA(B) receptor R1a subtype in transgenic mouse forebrain neurons would be sufficient to induce spontaneous absence seizures. As hypothesized, these transgenic mice develop spontaneous, recurrent, bilaterally synchronous, 3-6 Hz slow spike and wave discharges betwe...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2007.01.013

    authors: Wu Y,Chan KF,Eubanks JH,Guin Ting Wong C,Cortez MA,Shen L,Che Liu C,Perez Velazquez J,Tian Wang Y,Jia Z,Carter Snead O 3rd

    更新日期:2007-05-01 00:00:00

  • Functional genomics, genetic risk profiling and cell phenotypes in neurodegenerative disease.

    abstract::Human genetics provides unbiased insights into the causes of human disease, which can be used to create a foundation for effective ways to more accurately diagnose patients, stratify patients for more successful clinical trials, discover and develop new therapies, and ultimately help patients choose the safest and mos...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2020.105088

    authors: Finkbeiner S

    更新日期:2020-12-01 00:00:00

  • Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat.

    abstract::Environmental toxicants and, in particular, pesticides have been implicated as risk factors in Parkinson's disease (PD). The purpose of this study was to determine if selective nigrostriatal degeneration could be reproduced by systemic exposure of mice to the widely used herbicide paraquat. Repeated intraperitoneal pa...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.2002.0507

    authors: McCormack AL,Thiruchelvam M,Manning-Bog AB,Thiffault C,Langston JW,Cory-Slechta DA,Di Monte DA

    更新日期:2002-07-01 00:00:00

  • Anti-Abeta single-chain antibody delivery via adeno-associated virus for treatment of Alzheimer's disease.

    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

    authors: Fukuchi K,Tahara K,Kim HD,Maxwell JA,Lewis TL,Accavitti-Loper MA,Kim H,Ponnazhagan S,Lalonde R

    更新日期:2006-09-01 00:00:00

  • Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter.

    abstract::Mutations in the gene for DJ-1 have been associated with early-onset autosomal recessive parkinsonism. Previous studies of null DJ-1 mice have shown alterations in striatal dopamine (DA) transmission with no DAergic cell loss. Here we characterize a new line of DJ-1-deficient mice. A subtle locomotor deficit was prese...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2007.03.014

    authors: Manning-Boğ AB,Caudle WM,Perez XA,Reaney SH,Paletzki R,Isla MZ,Chou VP,McCormack AL,Miller GW,Langston JW,Gerfen CR,Dimonte DA

    更新日期:2007-08-01 00:00:00

  • Experimental models of amyotrophic lateral sclerosis.

    abstract::Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by the progressive loss of motor neurons, leading to profound weakness and eventual death of affected individuals. For the vast majority of patients with ALS, the etiology of the disorder is unknown, and although multiple clinical...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1006/nbdi.1999.0266

    authors: Elliott JL

    更新日期:1999-10-01 00:00:00

  • Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy.

    abstract::Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of glycine and γ-aminobutyric acid type-A receptors (GABAARs) at inhibitory synapses. An impairment of GABAergic synaptic inhibition represents a key pathway of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene have...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2014.02.001

    authors: Dejanovic B,Lal D,Catarino CB,Arjune S,Belaidi AA,Trucks H,Vollmar C,Surges R,Kunz WS,Motameny S,Altmüller J,Köhler A,Neubauer BA,Epicure Consortium,Nürnberg P,Noachtar S,Schwarz G,Sander T

    更新日期:2014-07-01 00:00:00

  • Prodegenerative IκBα expression in oligodendroglial α-synuclein models of multiple system atrophy.

    abstract::Multiple system atrophy is a progressive, neurodegenerative disease characterized by parkinsonism, ataxia, autonomic dysfunction, and accumulation of α-synuclein in oligodendrocytes. To understand how α-synuclein aggregates impact oligodendroglial homeostasis, we investigated an oligodendroglial cell model of α-synucl...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.12.002

    authors: Kragh CL,Gysbers AM,Rockenstein E,Murphy K,Halliday GM,Masliah E,Jensen PH

    更新日期:2014-03-01 00:00:00

  • Prostaglandin J2 reduces catechol-O-methyltransferase activity and enhances dopamine toxicity in neuronal cells.

    abstract::There is clear evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection and seizures, thus augmenting brain damage. Furthermore, chronic inflammation of the CNS is implicated in many neurodegenerative disorders. However, the effects of products of inflammation on neuronal ce...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2005.11.006

    authors: Ogburn KD,Bottiglieri T,Wang Z,Figueiredo-Pereira ME

    更新日期:2006-05-01 00:00:00

  • Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants.

    abstract::Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta) aggregates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. It was shown that A beta peptides (...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.1999.0241

    authors: Pereira C,Santos MS,Oliveira C

    更新日期:1999-06-01 00:00:00

  • Frataxin shows developmentally regulated tissue-specific expression in the mouse embryo.

    abstract::Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease caused either by an intronic GAA triplet repeat expansion that suppresses the expression of the frataxin gene on chromosome 9q13, or, rarely, by point mutations in the frataxin gene. We investigated the expression of the mouse frataxin homologue d...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.1997.0139

    authors: Jiralerspong S,Liu Y,Montermini L,Stifani S,Pandolfo M

    更新日期:1997-01-01 00:00:00

  • Hyperleucinemia causes hippocampal retromer deficiency linking diabetes to Alzheimer's disease.

    abstract::Type 2 diabetes (T2D) is a major risk factor for late-onset Alzheimer's disease (AD). A variety of metabolic changes related to T2D (e.g. hyperinsulinemia, hyperglycemia, and elevated branched-chain amino acids) have been proposed as mechanistic links, but the basis for this association remains unknown. Retromer-depen...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.12.017

    authors: Morabito MV,Berman DE,Schneider RT,Zhang Y,Leibel RL,Small SA

    更新日期:2014-05-01 00:00:00

  • A limited role for microglia in antibody mediated plaque clearance in APP mice.

    abstract::Amyloid-beta (Abeta) accumulation in senile plaques is a hallmark of Alzheimer's disease (AD). Immunotherapy is a leading approach for amyloid clearance, despite the early termination of the Elan clinical trial with active immunization due to a few cases of meningoencephalitis. The mechanisms of immunotherapy-mediated...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2007.07.019

    authors: Garcia-Alloza M,Ferrara BJ,Dodwell SA,Hickey GA,Hyman BT,Bacskai BJ

    更新日期:2007-12-01 00:00:00

  • Identification and functional dissection of localization signals within ataxin-3.

    abstract::Spinocerebellar ataxia type 3 (SCA3) or Machado-Joseph disease (MJD) belongs to a group of autosomal dominant neurodegenerative diseases, which are caused by the expansion of a polyglutamine repeat in the affected protein, in this case ataxin-3. Ataxin-3 is mainly localized in the cytoplasm; however, one hallmark of S...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2009.07.020

    authors: Antony PM,Mäntele S,Mollenkopf P,Boy J,Kehlenbach RH,Riess O,Schmidt T

    更新日期:2009-11-01 00:00:00

  • Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia.

    abstract::The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brai...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.01.008

    authors: Song CH,Bernhard D,Bolarinwa C,Hess EJ,Smith Y,Jinnah HA

    更新日期:2013-06-01 00:00:00

  • Chronic L-DOPA administration increases the firing rate but does not reverse enhanced slow frequency oscillatory activity and synchronization in substantia nigra pars reticulata neurons from 6-hydroxydopamine-lesioned rats.

    abstract::The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2016.02.003

    authors: Aristieta A,Ruiz-Ortega JA,Miguelez C,Morera-Herreras T,Ugedo L

    更新日期:2016-05-01 00:00:00

  • Preferential inactivation of Scn1a in parvalbumin interneurons increases seizure susceptibility.

    abstract::Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials in electrically excitable cells. Dominant mutations in SCN1A, which encodes the Nav1.1 VGSC α-subunit, underlie several forms of epilepsy, including Dravet syndrome (DS) and genetic epilepsy with febrile seizure...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.08.012

    authors: Dutton SB,Makinson CD,Papale LA,Shankar A,Balakrishnan B,Nakazawa K,Escayg A

    更新日期:2013-01-01 00:00:00

  • Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.

    abstract::Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsiv...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2014.10.012

    authors: Träger U,Andre R,Magnusson-Lind A,Miller JR,Connolly C,Weiss A,Grueninger S,Silajdžić E,Smith DL,Leavitt BR,Bates GP,Björkqvist M,Tabrizi SJ

    更新日期:2015-01-01 00:00:00

  • Peripheral hyperstimulation alters site of disease onset and course in SOD1 rats.

    abstract::In amyotrophic lateral sclerosis (ALS), the exogenous temporal triggers that result in initial motor neuron death are not understood. Overactivation and consequent accelerated loss of vulnerable motor neurons is one theory of disease initiation. The vulnerability of motor neurons in response to chronic peripheral nerv...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2010.03.021

    authors: Lepore AC,Tolmie C,O'Donnell J,Wright MC,Dejea C,Rauck B,Hoke A,Ignagni AR,Onders RP,Maragakis NJ

    更新日期:2010-09-01 00:00:00

  • A mouse model of the fragile X premutation: effects on behavior, dendrite morphology, and regional rates of cerebral protein synthesis.

    abstract::Carriers of FMR1 premutation alleles have 55-200 CGG repeats in the 5' untranslated region of the gene. These individuals are at risk for fragile X associated primary ovarian insufficiency (females) and, in late life, fragile X associated tremor and ataxia syndrome (males, and to a lesser extent, females). Premutation...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2011.01.008

    authors: Qin M,Entezam A,Usdin K,Huang T,Liu ZH,Hoffman GE,Smith CB

    更新日期:2011-04-01 00:00:00

  • Effect of a paraneoplastic cerebellar degeneration-associated neural protein on B-myb promoter activity.

    abstract::In this study, we have shown that a paraneoplastic cerebellar degeneration (PCD)-associated antigen, pcd17, binds to a cell cycle-related protein, MRG15. MRG15 derepresses the E2F-responsive B-myb promoter. The pcd17 antigen inhibits the derepression of the B-myb transcriptional activity by MRG15, and, as a result, pc...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2003.11.003

    authors: Sakai K,Kitagawa Y,Saiki S,Saiki M,Hirose G

    更新日期:2004-04-01 00:00:00

  • The IL-1beta system in epilepsy-associated malformations of cortical development.

    abstract::Focal cortical dysplasia (FCD) and glioneuronal tumors (GNT) are recognized causes of chronic intractable epilepsy. The cellular mechanism(s) underlying their epileptogenicity remain largely unknown. Compelling evidence in experimental models of seizures indicates an important role of interleukin (IL)-1beta in the mec...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2006.06.003

    authors: Ravizza T,Boer K,Redeker S,Spliet WG,van Rijen PC,Troost D,Vezzani A,Aronica E

    更新日期:2006-10-01 00:00:00

  • Neuroprotective effects of erythropoietin in the rat hippocampus after pilocarpine-induced status epilepticus.

    abstract::Neuroprotective functions of erythropoietin (Epo) are thought to involve a heteroreceptor composed of both Epo receptor (Epo-R) and common beta chain (betac). Here, we measured the response of hippocampal Epo system components (Epo, Epo-R and betac) during neurodegenerative processes following pilocarpine-induced stat...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2006.10.009

    authors: Nadam J,Navarro F,Sanchez P,Moulin C,Georges B,Laglaine A,Pequignot JM,Morales A,Ryvlin P,Bezin L

    更新日期:2007-02-01 00:00:00

  • Temporal lobe epilepsy causes selective changes in mu opioid and nociceptin receptor binding and functional coupling to G-proteins in human temporal neocortex.

    abstract::There is no information concerning signal transduction mechanisms downstream of the opioid/nociceptin receptors in the human epileptic brain. The aim of this work was to evaluate the level of G-proteins activation mediated by DAMGO (a mu receptor selective peptide) and nociceptin, and the binding to mu and nociceptin ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2009.06.008

    authors: Rocha L,Orozco-Suarez S,Alonso-Vanegas M,Villeda-Hernandez J,Gaona A,Páldy E,Benyhe S,Borsodi A

    更新日期:2009-09-01 00:00:00

  • Glut1 deficiency (G1D): epilepsy and metabolic dysfunction in a mouse model of the most common human phenotype.

    abstract::Brain glucose supplies most of the carbon required for acetyl-coenzyme A (acetyl-CoA) generation (an important step for myelin synthesis) and for neurotransmitter production via further metabolism of acetyl-CoA in the tricarboxylic acid (TCA) cycle. However, it is not known whether reduced brain glucose transporter ty...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.04.011

    authors: Marin-Valencia I,Good LB,Ma Q,Duarte J,Bottiglieri T,Sinton CM,Heilig CW,Pascual JM

    更新日期:2012-10-01 00:00:00

  • High t-PA release by neonate brain microvascular endothelial cells under glutamate exposure affects neuronal fate.

    abstract::Glutamate excitotoxicity is a consolidated hypothesis in neonatal brain injuries and tissue plasminogen activator (t-PA) participates in the processes through proteolytic and receptor mediated effects. In brain microvascular endothelial cell (nBMEC) cultures from neonates, t-PA content and release upon glutamate are h...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.10.020

    authors: Henry VJ,Lecointre M,Laudenbach V,Ali C,Macrez R,Jullienne A,Berezowski V,Carmeliet P,Vivien D,Marret S,Gonzalez BJ,Leroux P

    更新日期:2013-02-01 00:00:00