Abstract:
OBJECTIVE:Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. METHODS:Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. RESULTS:Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with α-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with β-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with α- and β-diversity. Physical inactivity and constipation were highest in individuals with the Firmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. INTERPRETATION:Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2020;88:320-331.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Heinzel S,Aho VTE,Suenkel U,von Thaler AK,Schulte C,Deuschle C,Paulin L,Hantunen S,Brockmann K,Eschweiler GW,Maetzler W,Berg D,Auvinen P,Scheperjans Fdoi
10.1002/ana.25788subject
Has Abstractpub_date
2020-08-01 00:00:00pages
320-331issue
2eissn
0364-5134issn
1531-8249journal_volume
88pub_type
杂志文章abstract::PINK1 was recently found to be associated with PARK6 as the causative gene. We performed mutation analysis in eight inbred families whose haplotypes link to the PARK6 region. We identified six pathogenic mutations (R246X, H271Q, E417G, L347P, and Q239X/R492X) in six unrelated families. All sites of mutations were nove...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20251
更新日期:2004-09-01 00:00:00
abstract:OBJECTIVE:Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25982
更新日期:2020-12-03 00:00:00
abstract::More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) [119] and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) [36]. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410160502
更新日期:1984-11-01 00:00:00
abstract::Because of the association of D-penicillamine (DP) therapy with myasthenia gravis, we have studied long-term DP treatment in five inbred strains of mice with doses comparable to those used in patients with rheumatoid arthritis. No clinical weakness or anti-acetylcholine receptor (AChR) antibody developed with up to 6 ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160103
更新日期:1984-07-01 00:00:00
abstract::Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease. However, the mechanisms by which activation of glutamate receptors produce parkinsonism are unknown. Therefore, we examined whether the glutamate agonists N-methyl-D-aspartate (NMDA), alpha-amino-3-hy...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410340413
更新日期:1993-10-01 00:00:00
abstract:OBJECTIVE:Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute hippocampal injury that evolves to HS. METHODS:FEBSTAT and 2 affiliated studies prospectively recruited 226 children ag...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.24081
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:To study antibody-independent contributions of B cells to inflammatory disease activity, and the immune consequences of B-cell depletion with rituximab, in patients with multiple sclerosis (MS). METHODS:B-Cell effector-cytokine responses were compared between MS patients and matched controls using a 3-signal...
journal_title:Annals of neurology
pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.21939
更新日期:2010-04-01 00:00:00
abstract::We describe 5 patients who presented with an acute cauda equina syndrome, which we believe was due to infarction of the conus medullaris. In 3 patients, the onset was spontaneous, and in 2 patients it was secondary to temporary occlusion of the distal aorta during medical manipulation. Pain in the buttocks and posteri...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410210510
更新日期:1987-05-01 00:00:00
abstract::Powerful new methods for imaging both brain anatomy and brain function are appearing at an increasing rate. The modern era of minimally invasive, highly informative, neurological diagnostic imaging methods began with the introduction of x-ray computed tomography in the 1970s. More recently, positron emission tomograph...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.410320316
更新日期:1992-09-01 00:00:00
abstract::A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) g...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410410222
更新日期:1997-02-01 00:00:00
abstract::We investigated the relationship between cerebral activity (measured with positron emission tomography) and word rate in normal subjects and aphasic patients listening to monosyllabic words at rates up to those encountered in normal speech. By measuring the slope of the regression of the individual activity-word rate ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10181
更新日期:2002-05-01 00:00:00
abstract::Progressive multifocal leukoencephalopathy is the most common clinical presentation of JC virus (JCV)-associated central nervous system (CNS) disease and has emerged as a major safety concern in multiple sclerosis patients treated with the monoclonal antibody natalizumab. Here we report clinical, radiological, and his...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23973
更新日期:2013-10-01 00:00:00
abstract::Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00
abstract::We previously reported that the monoclonal antibody Alz-50 recognizes a protein (A68) with an apparent molecular weight of 68,000 daltons in the brains of patients who died with Alzheimer's disease, but not in brain tissue from individuals free of neurological disease. We now report that substantial quantities of this...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410220412
更新日期:1987-10-01 00:00:00
abstract::A 30-year-old male drug abuser developed ophthalmoplegia, bulbar paralysis, and limb weakness responsive to edrophonium. However, potentiation of a low-amplitude evoked muscle action potential was produced with repetitive nerve stimulation at 10 Hz, and the clinical and electrophysiological data suggested the diagnosi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160314
更新日期:1984-09-01 00:00:00
abstract::Juvenile myoclonic epilepsy is a common type of idiopathic generalized epilepsy characterized by myoclonic, generalized tonic-clonic, and in 30% of patients, absence seizures. We studied a three-generation pedigree of 33 members, 10 of whom were clinically affected with juvenile myoclonic epilepsy or presented with su...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390208
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:The dose-response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy. METHODS:We have generated 3 lines of transgenic mice, expressing low, mid, and high levels of full-length human dysferlin from a muscle-specif...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21926
更新日期:2010-03-01 00:00:00
abstract::Serological evidence of either acute cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection was sought in a large series of patients with Guillain-Barré syndrome (GBS) and control subjects. Using an indirect immunofluorescent technique, IgM antibody directed against CMV was found in the serum of 33 of 220 GBS pat...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410090709
更新日期:1981-01-01 00:00:00
abstract::A patient is described who suffered a bilateral hemorrhagic infarction in the parasagittal cerebrum following neonatal asphyxia. This case confirms experimental results that show the parasagittal cerebrum is especially vulnerable to ischemic damage in newborns. ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410210215
更新日期:1987-02-01 00:00:00
abstract::The pharmacokinetics of levodopa (L-dopa) in plasma and in cisternal and lumbar cerebrospinal fluid (CSF) were studied in Rhesus monkeys that were given 2- to 3-hour intravenous infusions of L-dopa. Steady-state L-dopa concentrations in cisternal CSF correlated well with plasma levels, and yielded a CSF:plasma ratio o...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410270507
更新日期:1990-05-01 00:00:00
abstract::Two principal features of Alzheimer's disease (AD) are (1) the occurrence of neurofibrillary tangles (NFTs) and senile plaques, and (2) the loss of cortical cholinergic activity because of dysfunction of neurons in the basal forebrain cholinergic system. The relationship of these two abnormalities is an unresolved iss...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200407
更新日期:1986-10-01 00:00:00
abstract:OBJECTIVE:Determine the probability of attaining complete remission in children with nonsyndromic epilepsy (NSE) over the course of ≥10 years from initial diagnosis; identify early predictors of complete remission; and assess the risk of relapse after achieving complete remission. METHODS:In a prospective community-ba...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22461
更新日期:2011-10-01 00:00:00
abstract::A series of nine related aromatic monocarboxylic acids (ACAs) previously shown to inhibit muscle membrane chloride conductance (GCl) selectively in the rat were studied for their ability to produce myotonia. All nine induced characteristic repetitive electrical activity and delayed relaxation in isolated muscle, altho...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410040411
更新日期:1978-10-01 00:00:00
abstract:OBJECTIVE:To assess risk factors associated with care for stroke symptoms. METHODS:Using data from the population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) conducted January 25, 2003-February 28, 2007 (N = 23,664), we assessed care-seeking behavior among 3,668 participants w...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21357
更新日期:2008-04-01 00:00:00
abstract::Adult polyglucosan body disease (APBD) is a late-onset, slowly progressive disorder of the nervous system caused by glycogen branching enzyme (GBE) deficiency in a subgroup of patients of Ashkenazi Jewish origin. Similar biochemical finding is shared by glycogen storage disease type IV (GSD IV) that, in contrast to AP...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410440604
更新日期:1998-12-01 00:00:00
abstract::Averaged electroencephalographic activity related to rhythmic jerking movements was recorded in a patient with a complex neurological symptomatology. The diagnosis of a functional disorder was strongly suggested by his clinical course, inconsistent findings from physical examination, and negative workup. His abnormal ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200614
更新日期:1986-12-01 00:00:00
abstract:OBJECTIVE:Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safet...
journal_title:Annals of neurology
pub_type: 杂志文章,多中心研究
doi:10.1002/ana.25506
更新日期:2019-08-01 00:00:00
abstract::The accuracy of a variety of finger and color confrontation tests in identifying chiasmal and optic nerve visual field defects was assessed in patients whose field defects had been established beforehand by a conventional achromatic kinetic technique on the Goldmann perimeter. Kinetic and static finger confrontation m...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410100105
更新日期:1981-07-01 00:00:00
abstract::Early differential diagnosis of motor neuropathies (MN) and lower motor neuron diseases (LMND) is important, as prognosis and therapeutic approaches are different. We evaluated the diagnostic contribution of the biopsy of the motor branch of the obturator nerve and gracilis muscle in 21 consecutive patients in which, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22110
更新日期:2011-01-01 00:00:00
abstract::Nerve fibers containing neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP) were seen in the adventitia or at the adventitia-media border of the human temporal artery. Pharmacological experiments on isolated temporal artery segments revealed that ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200409
更新日期:1986-10-01 00:00:00