Abstract:
:Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer's disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively normal subjects and patients with other neurodegenerative disorders, we collected antemortem CSF samples from 66 AD patients and 25 patients with other neurodegenerative dementias followed longitudinally to neuropathologic confirmation, plus CSF from 33 cognitively normal subjects. We measured levels of 151 novel analytes via a targeted multiplex panel enriched in cytokines, chemokines and growth factors, as well as established AD CSF biomarkers (levels of Abeta42, tau and p-tau(181)). Two categories of biomarkers were identified: (1) analytes that specifically distinguished AD (especially CSF Abeta42 levels) from cognitively normal subjects and other disorders; and (2) analytes altered in multiple diseases (NrCAM, PDGF, C3, IL-1alpha), but not in cognitively normal subjects. A multi-prong analytical approach showed AD patients were best distinguished from non-AD cases (including cognitively normal subjects and patients with other neurodegenerative disorders) by a combination of traditional AD biomarkers and novel multiplex biomarkers. Six novel biomarkers (C3, CgA, IL-1alpha, I-309, NrCAM and VEGF) were correlated with the severity of cognitive impairment at CSF collection, and altered levels of IL-1alpha and TECK associated with subsequent cognitive decline in 38 longitudinally followed subjects with mild cognitive impairment. In summary, our targeted proteomic screen revealed novel CSF biomarkers that can improve the distinction between AD and non-AD cases by established biomarkers alone.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Hu WT,Chen-Plotkin A,Arnold SE,Grossman M,Clark CM,Shaw LM,Pickering E,Kuhn M,Chen Y,McCluskey L,Elman L,Karlawish J,Hurtig HI,Siderowf A,Lee VM,Soares H,Trojanowski JQdoi
10.1007/s00401-010-0667-0subject
Has Abstractpub_date
2010-06-01 00:00:00pages
669-78issue
6eissn
0001-6322issn
1432-0533journal_volume
119pub_type
杂志文章abstract::The authors present the case of a hypertensive patient with a thrombosis of a saccular microaneurysm (SMA) and underlying cerebral (pontine) lacunae. This SMA lay at the junction between the main vessel and two small feeding arteries penetrating into the necrotic territory. Microhemorrhages were observed in and outsid...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688313
更新日期:1986-01-01 00:00:00
abstract::Three cases of spontaneous olfactory neuroblastoma (ONB) in domestic cats were morphologically and immunocytochemically characterized. Diagnostic light microscopic features included Flexner and Homer-Wright rosettes, while ultrastructurally the cells had neuritic processes, intracellular intermediate filaments, and in...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294617
更新日期:1990-01-01 00:00:00
abstract::An autopsy case of unclassifiable presenil dementia is reported. The outstanding pathological findings were as follows; 1. presence of senile plaques, neurofibrillary changes, Pick bodies, Hirano bodies, granulovacuolar degeneration of neurons, etc. 2. numerous Lewy bodies in the brain stem and diencephalon, 3. peculi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685366
更新日期:1976-11-15 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00299415
更新日期:1992-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227767
更新日期:1993-01-01 00:00:00
abstract::Pontocerebellar hypoplasia type 2 (PCH-2; MIM 277470), an autosomal recessive neurodegeneration with fetal onset, was studied in six autopsies with ages at death ranging between 1 and 22 years. Three patients were distantly related. A case of olivopontocerebellar hypoplasia (OPCH; MIM 225753) was studied for compariso...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0263-0
更新日期:2007-10-01 00:00:00
abstract::An ultrastructural study was performed on normal and Benzo(a)-pyrene(B(a)P)-transformed fetal mouse brain cells. Early subcultures of a strain initiated from whole brain presented three cell types in vitro: astroglial, poorly differentiated glial, and spongioblastic types. After B(a)P-treatment, there was an exclusive...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690548
更新日期:1979-08-01 00:00:00
abstract::Axonal polyglucosan bodies in myelinated axons in the ventral posterolateral nucleus of the human thalamus (VPL) are described. These axonal inclusions were distributed exclusively in the dorsolateral part of the caudal VPL, and their arrangement may be associated with fibres originating from the gracile nucleus. They...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688332
更新日期:1987-01-01 00:00:00
abstract::Laquinimod (LAQ) is a new oral immunomodulatory compound that reduces relapse rate, brain atrophy and disability progression in multiple sclerosis (MS). LAQ has well-documented effects on inflammation in the periphery, but little is known about its direct activity within the central nervous system (CNS). To elucidate ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-012-1009-1
更新日期:2012-09-01 00:00:00
abstract::Investigations of the existence and distribution of muscle spindles and tendon organs in the human voluntary anal sphincter muscle in 53 cases of autopsy material from both female and male persons (age: 27th week of gestation to 81 years) brought forward the following results: Similar to animals, muscle spindles are f...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691860
更新日期:1984-01-01 00:00:00
abstract::The dynamics of cerebrospinal fluid (CSF) tau and Aβ biomarkers over time in Alzheimer's disease (AD) patients from prodromal pre-symptomatic to severe stages of dementia have not been clearly defined and recent studies, most of which are cross-sectional, present conflicting findings. To clarify this issue, we analyze...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-013-1151-4
更新日期:2013-11-01 00:00:00
abstract::Newborn rats were exposed to daily intraperitoneal injections of 10 mg lead nitrate per kg body weight for the first 15 postnatal days. The growth and mortality of the lead-exposed animals did not differ from their control litter-mates, injected with vehicle only. In our previous studies, focal hemorrhages and spongy ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687071
更新日期:1987-01-01 00:00:00
abstract::The kidney of a 7-month-old male Cairn terrier with globoid cell leukodystrophy (GLD) was investigated with light and electron microscopes. A few tubular epithelial cells in the inner medulla as well as some exfoliated cells in the lumina revealed PAS-positive cytoplasm in which needle-like structures were to be seen ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687036
更新日期:1986-01-01 00:00:00
abstract::This report deals with the expression of stress-response (heat-shock) protein 72 (srp 72) in a series of 95 primary human brain tumors and 21 carcinoma metastases to the central nervous system (CNS). Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 were used as positive con...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227818
更新日期:1992-01-01 00:00:00
abstract::An unusual tumor of the pituitary gland is reported. The most characteristic finding of the present tumor was the presence of numerous "colloid" and mucoid secretions. The cells were stellate in shape and there were intra- or intercellular lumina which were lined by many microvilli and occasional cilia. There were als...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687617
更新日期:1984-01-01 00:00:00
abstract::Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangle...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-016-1649-7
更新日期:2017-03-01 00:00:00
abstract::Morphometric observations have been made on the medial plantar division of the tibial nerve (MPD) and on the motor branches of the tibial nerve to the calf muscles (MBC) in rats ranging in age from weaning (3 weeks) to 12 months. Axon size, assessed by measurements of circumference and cross-sectional area, increased ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00308712
更新日期:1990-01-01 00:00:00
abstract::Hyper- and hypothyroidism repercussions on soma, nucleus and cytoplasm increases were studied by electron microscopy on 7-, 14-, 21-, and 35-day-old rats. Adult normal animals were compared with adult ones made hypothyroid until they were 35 days old. Also heat value restriction of food intake effects were compared wi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:
更新日期:1978-09-15 00:00:00
abstract::Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687379
更新日期:1989-01-01 00:00:00
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journal_title:Acta neuropathologica
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doi:10.1007/s00401-006-0114-4
更新日期:2006-09-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
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doi:10.1007/s00401-020-02133-x
更新日期:2020-05-01 00:00:00
abstract::The occurrence and topographic analysis of granulovacuolar degeneration (GVD) in the hippocampal cortex of mentally normal controls (75 cases) and patients with Alzheimer's dementia (AD; 17 cases which included Alzheimer's disease and senile dementia of Alzheimer type), multi-infarct dementia (MID; 16 cases), Pick's d...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00304627
更新日期:1992-01-01 00:00:00
abstract::Primary extradural ependymomas are rare neoplasms usually of the myxopapillary type. Reports on malignant primary extradural ependymal tumors are exceptionally rare. We here report on a 3-year-old boy with Schinzel-Giedion syndrome (SGS), who presented with lumbar spina bifida occulta and a progressive extraspinal les...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-006-0179-0
更新日期:2007-03-01 00:00:00
abstract::Astrocytic alpha-synuclein-immunoreactive inclusions have recently been noted to develop in sporadic Parkinson's disease (PD). Here, the presence of immunoreactive astrocytes is reported in 14 autopsy cases with clinically diagnosed PD and a neuropathological stage of 4 or higher. The labeled astrocytes occur preferen...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0244-3
更新日期:2007-09-01 00:00:00
abstract::Axons of the peripheral nervous system (PNS) are reduced in caliber in response to the experimental diabetic state. The cause of this reduced axonal size is disputed. Various theories include (a) axonal dwindling, (b) inhibition of growth, and (c) shrinkage due to serum hyperosmolarity. This study was designed to dire...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688637
更新日期:1985-01-01 00:00:00
abstract::The dynamics of cell-associated Concanavalin A (Con A) in astrocytes of the newborn rat (RNA), the rat glioma (AC), and the human glioblastoma (GB) were studied in vitro by fluorescence and electron microscopy. Con A receptors on the cell surface were seen usually as a continuous thin layer, and Con A accumulations in...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690804
更新日期:1982-01-01 00:00:00
abstract::This report concerns an immunocytochemical and ultrastructural study of the motor cortices of 11 patients with amyotrophic lateral sclerosis (ALS). Specimens from 12 normal individuals served as controls. Antibodies against phosphorylated neurofilament (PNF; 200 kDa), ubiquitin, glial fibrillary acidic protein (GFAP) ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00293318
更新日期:1994-01-01 00:00:00
abstract::Unusual inclusions with some of the features of "reducing bodies" were encountered in the skeletal muscle biopsy of a 2.5-year-old boy with childhood-onset acid maltase deficiency. The biopsy revealed a vacuolar myopathy with lysosomal storage of glycogen and eosinophilic refractile inclusions in myofibers, which appe...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00304641
更新日期:1992-01-01 00:00:00
abstract::Canine distemper virus (CDV) causes severe immunosuppression and neurological disease in dogs, associated with demyelination, and is a model for multiple sclerosis in man. In the early stage of the infection, demyelination is associated with viral replication in the white matter. In acute demyelinating lesions there i...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-004-0958-4
更新日期:2005-01-01 00:00:00