Abstract:
AIMS:Although telomere length (TL) and telomere maintenance proteins (shelterins) are markers of cellular senescence and peripheral blood biomarkers of Alzheimer's disease (AD), little information is available on telomeric alterations during the prodromal stage (MCI) of AD. We investigated TL in the default mode network (DMN), which underlies episodic memory deficits in AD, as well as shelterin protein and mRNA levels in the precuneus (PreC). METHODS:Telomere length was evaluated in DMN hubs and visual cortex using quantitative PCR (qPCR). In the PreC, western blotting and NanoString nCounter expression analyses evaluated shelterin protein and mRNA levels, respectively, in cases with an antemortem clinical diagnosis of no cognitive impairment (NCI), MCI and AD. RESULTS:TL was significantly reduced in the PreC in MCI and AD compared to NCI, but stable in frontal, inferior temporal, posterior cingulate and visual cortex. PreC TL correlated significantly with performance on cognitive tests. NCI cases with high vs low Braak scores displayed significantly shorter TL in posterior cingulate and frontal cortex, which correlated significantly with neuritic and diffuse amyloid-β plaque counts. Shelterin protein levels (TIN2, TRF1, TRF2 and POT1) declined in MCI and AD compared to NCI. The PreC displayed stable expression of shelterins TERF1, TERF2, POT1, RAP1 and TPP1, while TINF2 mRNA significantly increased in AD compared to NCI. CONCLUSIONS:These findings indicate a selective vulnerability to telomere attrition within different nodes of the DMN in prodromal AD and in aged NCI individuals with high Braak scores highlighting a putative role in the pathogenesis of AD.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Mahady LJ,He B,Malek-Ahmadi M,Mufson EJdoi
10.1111/nan.12672subject
Has Abstractpub_date
2020-10-26 00:00:00eissn
0305-1846issn
1365-2990pub_type
杂志文章abstract::Focal cortical dysplasia (FCD), which is often associated with intractable epilepsy, is a form of abnormal structure of the cerebral cortex caused by a disorder of normal neocortical development. In such cerebral lesions obtained from four patients (two male, two female; average age 32.3 years at operation), the immun...
journal_title:Neuropathology and applied neurobiology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2990.1999.00180.x
更新日期:1999-06-01 00:00:00
abstract::Diabetic neuropathy is probably the most common and one of the most disabling complications of diabetes mellitus. Although several possible pathogenetic mechanisms for this complication have been suggested, they cannot easily be tested in man. Therefore animal models with induced or spontaneous onset of diabetes melli...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00023.x
更新日期:1985-07-01 00:00:00
abstract::Cell death in gliomas may occur either by apoptosis, or, in the case of high grade tumours, by necrosis, but questions remain as to the pathogenesis and relationship between these processes. The development of cell death was investigated in multicellular glioma spheroid cultures. Spheroids model the development of cel...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.0305-1846.2001.00319.x
更新日期:2001-08-01 00:00:00
abstract:AIMS:Limb-girdle muscular dystrophy R9 (LGMDR9) is an autosomal recessive disorder caused by mutations in the fukutin-related protein gene (FKRP), encoding a glycosyltransferase involved in α-dystroglycan modification. Muscle atrophy, a significant feature of LGMDR9, occurs by a change in the normal balance between pro...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12684
更新日期:2020-12-18 00:00:00
abstract:AIM:Recent studies indicate that tau pathology in Alzheimer's disease (AD) does not initially manifest in the cerebral cortex but in selected subcortical nuclei, in particular the locus ceruleus (LC). In this study we correlate both olfactory and brainstem tau pathology with neuritic Braak stages. METHODS:We examined ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2011.01244.x
更新日期:2012-10-01 00:00:00
abstract::Serial sections of the brains of two cases with Alzheimer's disease were stained with the standard Bodian, modified Bielschowsky (reformed Gros-Schultze's modification) and thioflavin S methods. The numbers of demonstrated Alzheimer's neurofibrillary tangles (NFTs) were different between the two silver stains: from 15...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00677.x
更新日期:1986-01-01 00:00:00
abstract:AIMS:Wnt activation in medulloblastomas is associated with good outcome. Upfront testing and risk-adapted stratification of patients will be done in future clinical studies. In a cohort of 186 paediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup. ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12161
更新日期:2015-02-01 00:00:00
abstract::Ten minutes of total cerebral ischaemia was produced in normo- and hypoglycaemic rats. The most conspicuous findings were loss of hippocampal (CA-1) pyramidal cells and Purkinje cells, which were most pronounced in the normoglycaemic rats. While pre-ischaemic hypoglycaemia to some extent protected these cells, it led ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1981.tb00091.x
更新日期:1981-05-01 00:00:00
abstract::Neuronal loss is often quoted as an element of the pathology of the transmissible spongiform encephalopathies, but few data are published. To determine whether neuronal loss is a salient feature of murine scrapie, and whether there is a relationship with the other hallmark lesions of scrapie we compared the numbers of...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01027.x
更新日期:1995-02-01 00:00:00
abstract:AIMS:Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory autoimmune diseases that affect the central nervous system. Several genome-wide and candidate gene studies have identified genetic polymorphisms associated with the risk of MS or NMO. In particular, two recently published studies of meta-analy...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2012.01304.x
更新日期:2013-08-01 00:00:00
abstract::A case of congenital amaurotic idiocy, a subgroup of the neurovisceral lipidoses, is described. This is a rare condition of which only five cases have been reported previously. The brain was small and firm with marked neuronal loss and gliosis. Granular material with histochemical properties of the ceroid-lipofuscin g...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00041.x
更新日期:1985-11-01 00:00:00
abstract:AIMS:Clusterin is a topologically dynamic chaperone protein with the ability to participate in both intra- and extacellular proteostasis. Clusterin has been shown to be upregulated in the spinal cord of patients with amyotrophic lateral sclerosis (ALS) and has been shown to protect against TDP-43 protein misfolding in ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12575
更新日期:2020-04-01 00:00:00
abstract::Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Ad...
journal_title:Neuropathology and applied neurobiology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2990.1999.00188.x
更新日期:1999-08-01 00:00:00
abstract::Pathologists have been establishing archives of human organs and tissue for research use for many years now. Controversy has arisen recently over these collections, particularly with regard to the right of patients or relatives to consent to removal and retention of tissue, genetic research using stored tissue samples...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2990.2000.00276.x
更新日期:2000-10-01 00:00:00
abstract:AIMS:14,15-Epoxyeicosatrienoic acid (14,15-EET) is abundantly expressed in brain and exerts protective effects against ischaemia. 14,15-EET is hydrolysed by soluble epoxide hydrolase (sEH). sEH-/- mice show a higher level of 14,15-EET in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic con...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12291
更新日期:2016-12-01 00:00:00
abstract:AIMS:Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TAR...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12328
更新日期:2017-02-01 00:00:00
abstract::Herpes simplex virus was injected into the vitreous of suckling and adult rabbits. In the suckling rabbits the infection caused an arrested myelination of the strip. Further, the infected strips showed degenerative changes with splitting and distension of myelin sheaths which then disintegrated. Ultrastructurally, her...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1978.tb00530.x
更新日期:1978-01-01 00:00:00
abstract::Fibre type differentiation was carried out on 20 biopsies from Duchenne Muscular Dystrophy (DMD) sufferers using the acid-preincubated reaction for myofibrillar ATPase. Fibres, classified as either type 1, type 2 or 2C, were counted and their minimum diameters (least fibre axis) measured. Particular attention was paid...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00039.x
更新日期:1985-11-01 00:00:00
abstract::Two HIV-positive male patients presented with a variety of symptoms including hemiparesis, unsteadiness, progressive loss of vision and poor memory. There were multiple non-enhancing lesions shown by CT scan in the white matter of the cerebral hemispheres. Specimens obtained by burr-hole biopsy showed the features of ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1989.tb01242.x
更新日期:1989-09-01 00:00:00
abstract::Creutzfeldt-Jakob disease (CJD) is characterized by a loss of neurons accompanied by astrogliosis and spongiform changes in the neuropil. It has been recognized that reactive microglia occur in CJD but little is known about the regional distribution and extent of the microglial activation. We have, therefore, examined...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01097.x
更新日期:1995-12-01 00:00:00
abstract::In babies of low birth weight dying in the first week of life, bilirubin encephalopathy involving the thalamus only or the thalamus and one or two other areas occurred in nineteen of 376 cases examined over a 10 year period. Although coexistent germinal layer haemorrhage was present in sixteen, this was not thought to...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1983.tb00114.x
更新日期:1983-07-01 00:00:00
abstract::Inflammatory cells from the meninges of guinea-pigs with acute EAE have been isolated and quantitated. A mean of 7.5 x 10(6) cells were recovered from the brains of animals showing clinical signs of disease in contrast to only 1.5 x 10(6) cells in the controls. The immunological specificity of the meningeal inflammato...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1981.tb00082.x
更新日期:1981-03-01 00:00:00
abstract:AIMS:post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Its management is important in determining outcome. Although rodent hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not been...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2010.01118.x
更新日期:2011-02-01 00:00:00
abstract:AIM:Pilocytic astrocytomas represent the most common paediatric tumours of the central nervous system. Dissemination through the ventricular system occurs rarely in patients with pilocytic astrocytomas; however, it is more common in infants with diencephalic tumours, and is associated with a poor outcome. Despite histo...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12256
更新日期:2016-04-01 00:00:00
abstract:AIM:Levels of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) are robustly increased in spinal muscular atrophy (SMA) patient fibroblasts and mouse models. We therefore wanted to establish whether changes in UCHL1 contribute directly to disease pathogenesis, and to assess whether pharmacological inhibition of UCHL1 re...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12168
更新日期:2014-12-01 00:00:00
abstract::Sarcoplasmic masses contain disorganized myofibrillar material and are a striking feature of myotonic dystrophy. However their significance is still unclear. Using immunocytochemistry we studied the expression of cytoskeletal proteins (desmin and vimentin), dystrophin, markers of myogenic differentiation (foetal myosi...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00602.x
更新日期:2005-02-01 00:00:00
abstract:AIMS:Although modifications of the survival motor neurone gene are responsible for most spinal muscular atrophy (SMA) cases, the molecular pathophysiology and the muscular target proteins involved are still unknown. The aim of this study was to compare the expression of contractile and regulatory protein isoforms in qu...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2008.00950.x
更新日期:2008-12-01 00:00:00
abstract::Rats were given 2,5-hexanediol in their water for more than 5 weeks. The changes in the optic pathways were studied both qualitatively and quantitatively. Increase in 10-nm filaments within axons was noticeable from 10 days onwards in the superior colliculus and in the brachium of the superior colliculus. From then on...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1982.tb00298.x
更新日期:1982-07-01 00:00:00
abstract::Ultrastructural studies of spongiform encephalopathy (SE) reveal no very early pathological changes in kuru where membrane lamellation has been reported. This observation is challenged. In the later stages of SE, two main theories are examined--the spiroplasma theory and the prion (6 nm filament) theory. Neither are s...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00047.x
更新日期:1986-03-01 00:00:00
abstract:AIMS:Amyloid-β (Aβ) oligomers trigger synaptic degeneration that precedes plaque and tangle pathology. However, the signalling molecules that link Aβ oligomers to synaptic pathology remain unclear. Here, we addressed the potential role of RAPGEF2 as a novel signalling molecule in Aβ oligomer-induced synaptic and cognit...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12686
更新日期:2020-12-20 00:00:00