Abstract:
:Reductions in cerebral metabolism sufficient to impair cognition in normal individuals also occur in Alzheimer's disease (AD). The degree of clinical disability in AD correlates closely to the magnitude of the reduction in brain metabolism. Therefore, we tested whether impairments in tricarboxylic acid (TCA) cycle enzymes of mitochondria correlate with disability. Brains were from patients with autopsy-confirmed AD and clinical dementia ratings (CDRs) before death. Significant (p < 0.01) decreases occurred in the activities of the pyruvate dehydrogenase complex (-41%), isocitrate dehydrogenase (-27%), and the alpha-ketoglutarate dehydrogenase complex (-57%). Activities of succinate dehydrogenase (complex II) (+44%) and malate dehydrogenase (+54%) were increased (p < 0.01). Activities of the other four TCA cycle enzymes were unchanged. All of the changes in TCA cycle activities correlated with the clinical state (p < 0.01), suggesting a coordinated mitochondrial alteration. The highest correlation was with pyruvate dehydrogenase complex (r = 0.77, r2= 0.59). Measures to improve TCA cycle metabolism might benefit AD patients.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Bubber P,Haroutunian V,Fisch G,Blass JP,Gibson GEdoi
10.1002/ana.20474keywords:
subject
Has Abstractpub_date
2005-05-01 00:00:00pages
695-703issue
5eissn
0364-5134issn
1531-8249journal_volume
57pub_type
杂志文章abstract::Copper toxicity contributes to neuronal death in Wilson's disease and has been speculatively linked to the pathogenesis of Alzheimer's and prion diseases. We examined copper-induced neuronal death with the goal of developing neuroprotective strategies. Copper catalyzed an increase in hydroxyl radical generation in sol...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10276
更新日期:2002-08-01 00:00:00
abstract::A patient with generalized convulsions noted that seizures were reliably precipitated by mental arithmetic. The interictal electroencephalogram revealed only a mild, diffuse, nonspecific disturbance, but bursts of generalized epileptiform activity with no obvious clinical expression accompanied efforts at mental arith...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110609
更新日期:1982-06-01 00:00:00
abstract::Neurosurgical procedures such as the dorsal root entry zone operation, ganglionectomy, and spinal-cord stimulation have been offered to patients with intractable post-herpetic neuralgia (PHN). Poor efficacy or high morbidity have limited the overall usefulness of these procedures. We recently conducted a preliminary o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350716
更新日期:1994-01-01 00:00:00
abstract::Mutations of the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause autosomal recessive Charcot-Marie-Tooth disease type 4A. We report four additional families with recessive mutations (487C-->T, Q163X; 359G-->A, R120Q) of GDAP1; Q163X occurred in three unrelated Hispanic families that had the...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10505
更新日期:2003-03-01 00:00:00
abstract::Biochemical examinations of brain tissue samples obtained from patients with Alzheimer's disease have revealed a decreased quantity of the neurotransmitter acetylcholine and reduced activity of choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine formation. It has been suggested that the choline ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200214
更新日期:1986-08-01 00:00:00
abstract:OBJECTIVE:To identify novel autoantibodies for neuropathic pain (NeP). METHODS:We screened autoantibodies that selectively bind to mouse unmyelinated C-fiber type dorsal root ganglion (DRG) neurons using tissue-based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25279
更新日期:2018-08-01 00:00:00
abstract::Endoneurial fluid pressure (EFP) was recorded by an active, servo-null pressure system after a glass micropipette was inserted into rat sciatic nerve undergoing wallerian degeneration. The lesions were produced by crushing the left sciatic nerve of the anesthetized animal at its point of entry into the thigh. Eighty-f...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050610
更新日期:1979-06-01 00:00:00
abstract::Paired-helical filaments (PHFs) are an important diagnostic criterion of the inclusion-body myositis (IBM) muscle biopsy; but, until now, their presence could be identified only by electronmicroscopy. In this report, we describe an easy immunocytochemical procedure, utilizing commercially available antibody, that enab...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390318
更新日期:1996-03-01 00:00:00
abstract::We analyzed the prion protein gene (PRNP) region in patients with transmissible spongiform encephalopathy associated with the PRNP D178N mutation. The results suggest that the D178N chromosomes had independent origins in each affected pedigree or apparently sporadic case. A de novo spontaneous PRNP mutation was observ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10267
更新日期:2002-09-01 00:00:00
abstract::Gustatory sweating is an autonomic disorder that frequently occurs after parotid gland surgery. We investigated the action of intracutaneous injections of botulinum toxin (BTX) (1.0-2.0 mouse units/2.25-cm2 skin area) in 45 patients (mean age, 52 years) with gustatory sweating. The area of hyperhidrosis was determined...
journal_title:Annals of neurology
pub_type: 临床试验,杂志文章
doi:10.1002/ana.410420619
更新日期:1997-12-01 00:00:00
abstract::The value of various enhancement techniques as opposed to nonenhanced CT scanning was compared in 15 baboons with cerebral infarction secondary to embolization of the left middle cerebral artery. The most prominent CT findings in infarction included an area of low absorption in the opercula--basal ganglia--centrum sem...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050108
更新日期:1979-01-01 00:00:00
abstract::Intracranial abscesses are uncommon in the newborn. Observation of 2 infants and a review of the literature reveal that the offending organism was a Citrobacter in 12 of the 16 documented cases. In the Neonatal Meningitis Cooperative Study this organism was responsible for meningitis in only 4%. However, an analysis o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080308
更新日期:1980-09-01 00:00:00
abstract::Brains from male cases with dyslexia show symmetry of the planum temporale and predominantly left-sided cerebrocortical microdysgenesis. We now report on three women with dyslexia. In all brains, the planum temporale was again symmetrical. Also, in two of the brains, multiple foci of cerebrocortical glial scarring wer...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410280602
更新日期:1990-12-01 00:00:00
abstract::Gene therapy methods have continued to develop rapidly, and many initial limitations that hampered clinical application have been overcome. Thus serious consideration of clinical application of gene therapy is warranted for selected disorders in which the pathogenesis is well defined. Parkinson's disease has been the ...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.10654
更新日期:2003-01-01 00:00:00
abstract::Most neurodegenerative disorders are thought to result primarily from the accumulation of misfolded proteins, which interfere with protein homeostasis in neurons. For a subset of diseases, however, noncoding regions of RNAs assume a primary toxic gain-of-function, leading to degeneration in many tissues, including the...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21948
更新日期:2010-03-01 00:00:00
abstract::In Machado-Joseph disease (MJD) gene, there is a C/G polymorphism immediately after the CAG repeat; the expanded CAG repeat tract is exclusively followed by C, whereas about half of wild-type alleles are followed by G. Using this C/G polymorphism, we have engineered the small interfering RNA (siRNA) which decreased th...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20141
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to assess the distribution, frequency, and specific location of mutant huntingtin protein (mHTT) aggregates-the pathological hallmark of Huntington disease (HD)-within the various compartments of the spinal cord and their potential impact on the local vasculature and blood-spinal cord...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25107
更新日期:2017-12-01 00:00:00
abstract::A family with Gerstmann-Sträussler-Scheinker disease had coincidental clinical onset in three members of two generations, a phenomenon suggesting a common source of a transmissible agent. A regular dietary supplement in this family was home-bred rabbit. The clinical picture, although generally similar to that in previ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140611
更新日期:1983-12-01 00:00:00
abstract::Three young adults with intractable complex partial seizures were studied by electroencephalography, magnetoencephalography, and electrocorticography. Interictal electroencephalographic (EEG) spikes for each patient were grouped according to their morphological characteristics and distribution across channels. Mapping...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220311
更新日期:1987-09-01 00:00:00
abstract::A patient with recessive generalized congenital myotonia and severe, disabling weakness underwent various forms of treatment while being monitored electrophysiologically. Phenytoin, verapamil, and acetazolamide were ineffective, but tocainide yielded good results. Improvement was dose-dependent, and was limited by irr...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410190515
更新日期:1986-05-01 00:00:00
abstract::The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivit...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220607
更新日期:1987-12-01 00:00:00
abstract::Intravenous bolus administration of oxygen 15-labeled water and positron emission tomography were used to measure changes in brain blood flow induced by two modes of photic stimuli over a wide range of repetition rates. These stimuli (patterned-flash and reversing checkerboard) were chosen in order to determine whethe...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410170315
更新日期:1985-03-01 00:00:00
abstract:OBJECTIVE:C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD). We examined aging trajectories of cortical thickness (CTh) and surface area in C9orf72 expansion adult carriers compared to healthy controls to characterize preclinical cerebral changes leading to symptoms. METHODS:Data were...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25748
更新日期:2020-07-01 00:00:00
abstract::By most measures, academic neurology is thriving as never before, yet convening forces are changing the face of academic neurology. This report focuses on changes that academic neurology and the American Neurological Association could undertake to seize new opportunities and resist damaging potential changes. These pr...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390604
更新日期:1996-06-01 00:00:00
abstract::We report FK506-induced neurotoxicity in 14 of 44 consecutive patients following orthoptic liver transplantation. In 10 of these 14 patients, postural hand tremors were found in the first weeks following surgery, transient apraxia of speech in 3, and generalized tonic-clonic seizures were noted in 2 patients. Other ma...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350422
更新日期:1994-04-01 00:00:00
abstract:OBJECTIVE:Degeneration of chronically demyelinated axons is a major cause of irreversible neurological decline in the human central nervous system disease, multiple sclerosis (MS). Although the molecular mechanisms responsible for this axonal degeneration remain to be elucidated, dysfunction of axonal Na+/K+ ATPase is ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21381
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVE:Migraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated CaV 2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV 2.1 channels and a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24449
更新日期:2015-08-01 00:00:00
abstract::We report on a 12-year-old girl with a severe subacute to chronic bifrontal leukoencephalopathy. By clinical, biochemical, radiological, and neuropathological criteria, a diagnosis of inflammatory myelinoclastic diffuse sclerosis was reached. This is the third fully documented case. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410230422
更新日期:1988-04-01 00:00:00
abstract::Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N-acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390111
更新日期:1996-01-01 00:00:00
abstract::Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated proteins can induce an...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00