Abstract:
OBJECTIVES:Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of soluble Abeta(42) between brain and CSF. We investigated this hypothesis. METHODS:We compared the in vivo brain amyloid load (via positron emission tomography imaging of the amyloid-binding agent, Pittsburgh Compound-B [PIB]) with CSF Abeta(42) and other measures (via enzyme-linked immunosorbent assay) in clinically characterized research subjects. RESULTS:Subjects fell into two nonoverlapping groups: those with positive PIB binding had the lowest CSF Abeta(42) level, and those with negative PIB binding had the highest CSF Abeta(42) level. No relation was observed between PIB binding and CSF Abeta(40), tau, phospho-tau(181), plasma Abeta(40), or plasma Abeta(42). Importantly, PIB binding and CSF Abeta(42) did not consistently correspond with clinical diagnosis; three cognitively normal subjects were PIB-positive with low CSF Abeta(42), suggesting the presence of amyloid in the absence of cognitive impairment (ie, preclinical AD). INTERPRETATION:These observations suggest that brain amyloid deposition results in low CSF Abeta(42), and that amyloid imaging and CSF Abeta(42) may potentially serve as antecedent biomarkers of (preclinical) AD.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Fagan AM,Mintun MA,Mach RH,Lee SY,Dence CS,Shah AR,LaRossa GN,Spinner ML,Klunk WE,Mathis CA,DeKosky ST,Morris JC,Holtzman DMdoi
10.1002/ana.20730keywords:
subject
Has Abstractpub_date
2006-03-01 00:00:00pages
512-9issue
3eissn
0364-5134issn
1531-8249journal_volume
59pub_type
杂志文章abstract::Malignant tumors are known to have a "remote" or nonmetastatic effect on the central and peripheral nervous systems. Eight patients were seen with proximal muscle weakness in association with bronchogenic carcinoma (5), carcinoma of breast (2), and leukemia (1). Electromyography demonstrated small polyphasic motor uni...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040314
更新日期:1978-09-01 00:00:00
abstract::Alterations of nodal and paranodal axolemma of the rat sciatic nerve were investigated in antigalactocerebroside serum-induced demyelination. A ferric ion-ferrocyanide (FeFCN) stain that appears to stain the regions with a high sodium channel density in nerve fibers was applied. When acute conduction block was initiat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150611
更新日期:1984-06-01 00:00:00
abstract:OBJECTIVE:Loss of function mutations in PINK1 typically lead to early onset Parkinson disease (PD). Zebrafish (Danio rerio) are emerging as a powerful new vertebrate model to study neurodegenerative diseases. We used a pink1 mutant (pink(-/-) ) zebrafish line with a premature stop mutation (Y431*) in the PINK1 kinase d...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23999
更新日期:2013-12-01 00:00:00
abstract::In this study, we preincubated the sera of 3 patients with neuropathies associated with elevated titers of IgM anti-GM1 antibodies, with increasing concentrations of intravenous Ig (IVIg) and assayed the inhibitory effect of this mixture on antibody binding to immobilized GM1 by an enzyme-linked immunosorbent assay. P...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390121
更新日期:1996-01-01 00:00:00
abstract::Recent studies have indicated a normal gene dose for the amyloid precursor protein (APP) in Alzheimer's disease (AD). These findings leave open the possibility that elevated levels of messenger RNA (mRNA) for this protein may contribute to the pathogenesis of AD. Using Northern analysis, we compared the levels of mRNA...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410250404
更新日期:1989-04-01 00:00:00
abstract:OBJECTIVE:There are no validated methods for predicting the timing of seizures. Using machine learning, we sought to forecast 24-hour risk of self-reported seizure from e-diaries. METHODS:Data from 5,419 patients on SeizureTracker.com (including seizure count, type, and duration) were split into training (3,806 patien...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25812
更新日期:2020-09-01 00:00:00
abstract:OBJECTIVE:Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutation...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24410
更新日期:2015-07-01 00:00:00
abstract::In a patient with acquired immunodeficiency disease syndrome (AIDS) and muscle weakness, a muscle biopsy specimen disclosed degeneration of muscle fibers, regeneration, and focal endomysial mononuclear inflammation. A conspicuous feature was the presence of perivascular macrophages within the endomysium that showed po...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410280418
更新日期:1990-10-01 00:00:00
abstract::Dopamine transporter messenger RNA (mRNA) expression was assessed by in situ hybridization over individual pigmented neurons from the substantia nigra pars compacta in midbrain sections from 7 parkinsonian and 7 age-matched, neurologically normal patients. In the normal control brains, high levels of expression of dop...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350421
更新日期:1994-04-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410270214
更新日期:1990-02-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410370416
更新日期:1995-04-01 00:00:00
abstract::We report biochemical, immunological, and morphological findings in a patient with fatal Kearns-Sayre syndrome. Histochemical and biochemical findings from muscle biopsy specimens obtained 7 years apart documented the disease's evolution from a mild mitochondrial disorder affecting a small proportion of muscle fibers ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410210607
更新日期:1987-06-01 00:00:00
abstract::The possibility of detecting acute hypoxic-ischemic brain lesions by prenatal magnetic resonance imaging or ultrasound is low. We present a case of a fetus with a vein of Galen arteriovenous malformation in whom prenatal diffusion-weighted magnetic resonance imaging at 33 weeks of gestation clearly detected cerebral a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10255
更新日期:2002-08-01 00:00:00
abstract:OBJECTIVE:Acquired epilepsy is a devastating long-term risk of various brain insults, including trauma, stroke, infections, and status epilepticus (SE). There is no preventive treatment for patients at risk. Attributable to the complex alterations involved in epileptogenesis, it is likely that multitargeted approaches ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24804
更新日期:2016-12-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030302
更新日期:1978-03-01 00:00:00
abstract::Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both tra...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350507
更新日期:1994-05-01 00:00:00
abstract::The etiology of sudden death in patients with epilepsy remains unclear. Previous studies in a well-established sheep model of status epilepticus showed that more than one-third of the unsedated animals died within 5 minutes of seizure onset due to hypoventilation. The relative contributions of airway obstruction and c...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410420409
更新日期:1997-10-01 00:00:00
abstract::In an attempt to define prognostic indicators of intelligence and seizures in the hemiparetic cerebral palsy population, birth histories, electroencephalograms, and computerized tomographic (CT) scans were reviewed in 52 children with hemiparetic cerebral palsy. Cases were excluded when the hemiparesis might have been...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410090407
更新日期:1981-04-01 00:00:00
abstract:OBJECTIVE:Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course? METHODS:To identify possible biomarkers linking meningeal inflammat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25197
更新日期:2018-04-01 00:00:00
abstract::A brief description is given of neurofibrillary changes of the paired helical filament type in a variety of chronic neurological diseases. These include subacute sclerosing panencephalitis, lead encephalopathy, tuberous sclerosis, Down syndrome, Hallervorden-Spatz disease, and lipofuscinosis. In these conditions, with...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410050311
更新日期:1979-03-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410130620
更新日期:1983-06-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410230717
更新日期:1988-01-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10806
更新日期:2004-01-01 00:00:00
abstract::Patients with multiple sclerosis (MS) frequently have selective depletion of the CD45R+CD4+ T-cell subset during active phases of disease. To study the relationship between changes in this subset and the onset of objective clinical exacerbations of disease, a longitudinal study was undertaken. Two CD4+ T-cell subsets ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410240204
更新日期:1988-08-01 00:00:00
abstract:OBJECTIVE:Accumulation of mitochondrial DNA (mtDNA) damage has been associated with aging and abnormal oxidative metabolism. We hypothesized that in human immunodeficiency virus-associated sensory neuropathy (HIV-SN), damaged mtDNA accumulates in distal nerve segments, and that a spatial pattern of mitochondrial dysfun...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22150
更新日期:2011-01-01 00:00:00
abstract::The North American study of plasmapheresis in Guillain-Barré syndrome (GBS) included early, standardized electrodiagnostic testing in 210 of the 245 patients. To determine the types of abnormalities and the relation to outcome, we analyzed the prospectively collected motor conduction data obtained during the first 30 ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410230407
更新日期:1988-04-01 00:00:00
abstract::Nine patients who had suffered strokes were examined between 10 and 34 days after onset using positron emission tomography. DMO labeled with carbon 11 was used to evaluate brain acid-base balance, and the oxygen-15 inhalation technique was used to measure regional cerebral blood flow, the oxygen extraction fraction, a...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410140405
更新日期:1983-10-01 00:00:00
abstract::An artificial system is described in which anti-dinitrophenyl (DNP) antibody attaches to hapten-conjugated human brain tissue. Treatment of this material with acetic acid at pH 2.5 to 3.0 for 90 seconds followed by immediate neutralization results in dissociation of antibody from the hapten-conjugated brain. Less than...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410030507
更新日期:1978-05-01 00:00:00
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journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20060
更新日期:2004-04-01 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