Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI.


:The close correlation between abnormally low pre-mortem cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ(1-42)) and plaque burden measured by amyloid imaging as well as between pathologically increased levels of CSF tau and the extent of neurodegeneration measured by MRI has led to growing interest in using these biomarkers to predict the presence of AD plaque and tangle pathology. A challenge for the widespread use of these CSF biomarkers is the high variability in the assays used to measure these analytes which has been ascribed to multiple pre-analytical and analytical test performance factors. To address this challenge, we conducted a seven-center inter-laboratory standardization study for CSF total tau (t-tau), phospho-tau (p-tau(181)) and Aβ(1-42) as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Aliquots prepared from five CSF pools assembled from multiple elderly controls (n = 3) and AD patients (n = 2) were the primary test samples analyzed in each of three analytical runs by the participating laboratories using a common batch of research use only immunoassay reagents (INNO-BIA AlzBio3, xMAP technology, from Innogenetics) on the Luminex analytical platform. To account for the combined effects on overall precision of CSF samples (fixed effect), different laboratories and analytical runs (random effects), these data were analyzed by mixed-effects modeling with the following results: within center %CV 95% CI values (mean) of 4.0-6.0% (5.3%) for CSF Aβ(1-42); 6.4-6.8% (6.7%) for t-tau and 5.5-18.0% (10.8%) for p-tau(181) and inter-center %CV 95% CI range of 15.9-19.8% (17.9%) for Aβ(1-42), 9.6-15.2% (13.1%) for t-tau and 11.3-18.2% (14.6%) for p-tau(181). Long-term experience by the ADNI biomarker core laboratory replicated this degree of within-center precision. Diagnostic threshold CSF concentrations for Aβ(1-42) and for the ratio t-tau/Aβ(1-42) were determined in an ADNI independent, autopsy-confirmed AD cohort from whom ante-mortem CSF was obtained, and a clinically defined group of cognitively normal controls (NCs) provides statistically significant separation of those who progressed from MCI to AD in the ADNI study. These data suggest that interrogation of ante-mortem CSF in cognitively impaired individuals to determine levels of t-tau, p-tau(181) and Aβ(1-42), together with MRI and amyloid imaging biomarkers, could replace autopsy confirmation of AD plaque and tangle pathology as the "gold standard" for the diagnosis of definite AD in the near future.


Acta Neuropathol


Acta neuropathologica


Shaw LM,Vanderstichele H,Knapik-Czajka M,Figurski M,Coart E,Blennow K,Soares H,Simon AJ,Lewczuk P,Dean RA,Siemers E,Potter W,Lee VM,Trojanowski JQ,Alzheimer's Disease Neuroimaging Initiative.




Has Abstract


2011-05-01 00:00:00












  • FOCAD loss impacts microtubule assembly, G2/M progression and patient survival in astrocytic gliomas.

    abstract::In search of novel genes associated with glioma pathogenesis, we have previously shown frequent deletions of the KIAA1797/FOCAD gene in malignant gliomas, and a tumor suppressor function of the encoded focadhesin impacting proliferation and migration of glioma cells in vitro and in vivo. Here, we examined an associati...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Brand F,Förster A,Christians A,Bucher M,Thomé CM,Raab MS,Westphal M,Pietsch T,von Deimling A,Reifenberger G,Claus P,Hentschel B,Weller M,Weber RG

    更新日期:2020-01-01 00:00:00

  • Unmyelinated nerve fibres in feline acrylamide neuropathy.

    abstract::Electronmicroscope studies have been performed on the greater splanchnic nerve and the nerve to the medial head of gastrocnemius muscle of control and acrylamide poisoned cats. Degeneration of unmyelinated as well as of myelinated fibres was observed in both nerves. In cats severely poisoned with acrylamide, some very...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Post EJ

    更新日期:1978-04-26 00:00:00

  • Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease.

    abstract::Pelizaeus-Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood-brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary cholesterol in two PMD patients did not lead to a major ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Stumpf SK,Berghoff SA,Trevisiol A,Spieth L,Düking T,Schneider LV,Schlaphoff L,Dreha-Kulaczewski S,Bley A,Burfeind D,Kusch K,Mitkovski M,Ruhwedel T,Guder P,Röhse H,Denecke J,Gärtner J,Möbius W,Nave KA,Saher G

    更新日期:2019-07-01 00:00:00

  • Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling.

    abstract::Activating beta-catenin mutations with aberrant cytoplasmic and nuclear protein accumulation are hallmarks of adamantinomatous craniopharyngiomas (adaCP). These tumours tend to be associated with unfavourable and occasionally disastrous sequelae, as they invade adjacent brain structures such as the hypothalamus. The p...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Hölsken A,Buchfelder M,Fahlbusch R,Blümcke I,Buslei R

    更新日期:2010-05-01 00:00:00

  • Active, phosphorylation-dependent MAP kinases, MAPK/ERK, SAPK/JNK and p38, and specific transcription factor substrates are differentially expressed following systemic administration of kainic acid to the adult rat.

    abstract::Excitotoxicity is considered a major cell death inductor in neurodegeneration. Yet the mechanisms involved in cell death and cell survival following excitotoxic insults are poorly understood. Expression of active, phosphorylation-dependent mitogen-activated extracellular signal-regulated kinases (MAPK/ERKs), stress-ac...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Ferrer I,Blanco R,Carmona M,Puig B,Domínguez I,Viñals F

    更新日期:2002-04-01 00:00:00

  • Multiple sclerosis and amyloid deposits in the white matter of the brain.

    abstract::We present the neuropathological findings in a female patient with clinically definite multiple sclerosis (MS), who at autopsy had multifocal amyloid deposits in the white matter of the brain without other signs of amyloidosis. The patient had relapsing/remitting MS between the ages of 26 and 45, and during her last 1...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,评审


    authors: Nennesmo I,Bogdanovic N,Petrén AL,Fredrikson S

    更新日期:1997-02-01 00:00:00

  • Correction to: Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials.

    abstract::The original version of this article unfortunately contained a typesetting error in Fig 3c. The corrected Fig. 3 is given in the following page. ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,已发布勘误


    authors: Liu APY,Gudenas B,Lin T,Orr BA,Klimo P Jr,Kumar R,Bouffet E,Gururangan S,Crawford JR,Kellie SJ,Chintagumpala M,Fisher MJ,Bowers DC,Hassall T,Indelicato DJ,Onar-Thomas A,Ellison DW,Boop FA,Merchant TE,Robinson GW,N

    更新日期:2020-02-01 00:00:00

  • Embryonal neuroepithelial tumors induced by human adenovirus type 12 in rodents. 1. Tumor induction in the peripheral nervous system.

    abstract::Human adenovirus type 12 (Ad 12) was inoculated intraperitoneally, intrapleurally, intramuscularly or subcutaneously into newborn rodents. Tumors developed preferentially in the peritoneal cavities in 93.9% of the hamsters and 82.6% of the mice, but none in rats; in contrast to the high incidence of brain tumors in ra...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Ogawa K

    更新日期:1989-01-01 00:00:00

  • Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy.

    abstract::Neuronal accumulation of oligomeric amyloid-beta (Alphabeta) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Abeta stress to neurons by immigration into the brain and phagocytosis of Alphabeta. We tested migration and export across a blood-br...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Zaghi J,Goldenson B,Inayathullah M,Lossinsky AS,Masoumi A,Avagyan H,Mahanian M,Bernas M,Weinand M,Rosenthal MJ,Espinosa-Jeffrey A,de Vellis J,Teplow DB,Fiala M

    更新日期:2009-02-01 00:00:00

  • Gamma-enolase and glial fibrillary acidic protein in nervous system tumors. An immunohistochemical study using specific monoclonal antibodies.

    abstract::A large series of central and peripheral nervous system tumors was studied for the presence of glial fibrillary acidic protein (GFAP) and gamma-enolase (neuron-specific enolase, NSE), using specific monoclonal antibodies (mAbs). Occurrence in and specificity of GFAP to glial and mixed tumors was confirmed and depended...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Cras P,Martin JJ,Gheuens J

    更新日期:1988-01-01 00:00:00

  • Ultrastructural study of medullomyoblastoma.

    abstract::A case of cerebellar medullomyoblastoma in a young boy was investigated by electron microscopy. The neuroectodermal component shows the characteristics of a desmoplastic medulloblastoma. The mesodermal component consists of more or less differentiated cross-striated muscle cells. Undifferentiated muscle cells are very...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Walter GF,Brucher JM

    更新日期:1979-12-01 00:00:00

  • Subclinical entrapment neuropathy of the equine suprascapular nerve.

    abstract::The suprascapular nerve from 14 horses, which had no clinical evidence of spinatus muscle atrophy, were obtained to determine whether the nerve was sub-clinically compressed at the scapular edge. The nerves were divided into three portions, proximal and distal to the scapular edge and as it reflected around it. In nin...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Duncan ID,Schneider RK,Hammang JP

    更新日期:1987-01-01 00:00:00

  • "Reducing body"-like inclusions in skeletal muscle in childhood-onset acid maltase deficiency.

    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


    authors: Jay V,Christodoulou J,Mercer-Connolly A,McInnes RR

    更新日期:1992-01-01 00:00:00

  • Apoptosis of oligodendrocytes occurs for long distances away from the primary injury after compression trauma to rat spinal cord.

    abstract::We evaluated by in situ nick end labeling the presence of apoptotic glial cells in the spinal cord of rats which have sustained a moderate and severe compression injury at the level of T8-9, resulting in a severe but reversible paraparesis and irreversible paraplegia, respectively. In a previous investigation we found...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Li GL,Farooque M,Holtz A,Olsson Y

    更新日期:1999-11-01 00:00:00

  • Expression of the intermediate filament protein synemin in myofibrillar myopathies and other muscle diseases.

    abstract::Synemin is a member of the intermediate protein superfamily. Previous studies in avian and rodent skeletal and cardiac muscles have demonstrated that synemin localises at the Z-band, where it associates with desmin and alpha-actinin. In the present study, the distribution of synemin was examined using immunohistochemi...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Olivé M,Goldfarb L,Dagvadorj A,Sambuughin N,Paulin D,Li Z,Goudeau B,Vicart P,Ferrer I

    更新日期:2003-07-01 00:00:00

  • Dysferlin expression in tubular aggregates: their possible relationship to endoplasmic reticulum stress.

    abstract::Dysferlin is a newly identified sarcolemmal protein related to Miyoshi myopathy and limb-girdle muscular dystrophy. Although its function is still unknown, it is inferred from the presence of C2 domains and a transmembrane domain in its sequence that dysferlin may be expressed or located not only at the sarcolemma but...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Ikezoe K,Furuya H,Ohyagi Y,Osoegawa M,Nishino I,Nonaka I,Kira J

    更新日期:2003-06-01 00:00:00

  • Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins.

    abstract::Bundles of paired helical filaments (PHF) accumulate in the pyramidal neurons that degenerate during Alzheimer's disease. This neurofibrillary degeneration is highly correlated with clinical signs of dementia. During the degenerating process, Tau proteins, which are the major antigenic components of PHF, are abnormall...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Delacourte A,Flament S,Dibe EM,Hublau P,Sablonnière B,Hémon B,Shérrer V,Défossez A

    更新日期:1990-01-01 00:00:00

  • Morphological assessment of ethyl choline mustard aziridinium-induced neurotoxicity in rat brain reaggregate cultures.

    abstract::Foetal rat brain reaggregate cultures have been employed to investigate the morphological changes associated with the neurotoxic action of ethylcholine mustard aziridinium (ECMA). In a companion study we provided evidence for apparent selective cholinergic neurotoxicity. Exposure of 9-day-old cultures to 12.5 microM E...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Jones HB,Pillar AM,Prince AK

    更新日期:1993-01-01 00:00:00

  • WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism?

    abstract::Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Mehling M,Simon P,Mittelbronn M,Meyermann R,Ferrone S,Weller M,Wiendl H

    更新日期:2007-08-01 00:00:00

  • Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma.

    abstract::Missense mutations of the V600E type constitute the vast majority of tumor-associated somatic alterations in the v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) gene. Initially described in melanoma, colon and papillary thyroid carcinoma, these alterations have also been observed in primary nervous system tumors...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Schindler G,Capper D,Meyer J,Janzarik W,Omran H,Herold-Mende C,Schmieder K,Wesseling P,Mawrin C,Hasselblatt M,Louis DN,Korshunov A,Pfister S,Hartmann C,Paulus W,Reifenberger G,von Deimling A

    更新日期:2011-03-01 00:00:00

  • Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium.

    abstract::When 22 members of the BrainNet Europe (BNE) consortium assessed 31 cases with alpha-synuclein (alphaS) immunoreactive (IR) pathology applying the consensus protocol described by McKeith and colleagues in 2005, the inter-observer agreement was 80%, being lowest in the limbic category (73%). When applying the staging p...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Alafuzoff I,Ince PG,Arzberger T,Al-Sarraj S,Bell J,Bodi I,Bogdanovic N,Bugiani O,Ferrer I,Gelpi E,Gentleman S,Giaccone G,Ironside JW,Kavantzas N,King A,Korkolopoulou P,Kovács GG,Meyronet D,Monoranu C,Parchi P,Park

    更新日期:2009-06-01 00:00:00

  • Topographic distribution of scrapie amyloid-immunoreactive plaques in chronic wasting disease in captive mule deer (Odocoileus hemionus hemionus).

    abstract::Chronic wasting disease (CWD), a progressive neurological disorder of captive mule deer, black-tailed deer, hybrids of mule deer and white-tailed deer and Rocky Mountain elk, is characterized neuropathologically by widespread spongiform change of the neuropil, intracytoplasmic vacuolation in neuronal perikarya and ast...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Guiroy DC,Williams ES,Yanagihara R,Gajdusek DC

    更新日期:1991-01-01 00:00:00

  • Mixed multiple system atrophy and progressive supranuclear palsy: a clinical and pathological report of one case.

    abstract::We report a patient who showed pathological features of both multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) at autopsy. The clinical features included severe cerebellar ataxia, autonomic failure, and rigid-akinetic parkinsonism. The clinical diagnosis was MSA. Pathological examination showed se...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Takanashi M,Ohta S,Matsuoka S,Mori H,Mizuno Y

    更新日期:2002-01-01 00:00:00

  • Differential expression of intercellular adhesion molecule-1 (ICAM-1) in the A beta-containing lesions in brains of patients with dementia of the Alzheimer type.

    abstract::Inflammatory processes have been implicated in the formation of senile plaques in the cerebral cortex of patients with dementia of the Alzheimer type (DAT), since several inflammation-induced proteins are present within these plaques. The relation between inflammatory components and other amyloid beta protein (A beta)...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Verbeek MM,Otte-Höller I,Wesseling P,Ruiter DJ,de Waal RM

    更新日期:1996-01-01 00:00:00

  • Constant and severe involvement of Betz cells in corticobasal degeneration is not consistent with pyramidal signs: a clinicopathological study of ten autopsy cases.

    abstract::This report concerns a clinicopathological study of three additional patients with corticobasal degeneration (CBD), described here for the first time, and a clinicopathological correlation between pyramidal signs and upper motor neuron involvement, in ten autopsy cases of CBD, including seven cases reported by us prev...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,评审


    authors: Tsuchiya K,Murayama S,Mitani K,Oda T,Arima K,Mimura M,Nagura H,Haga C,Akiyama H,Yamanouchi H,Mizusawa H

    更新日期:2005-04-01 00:00:00

  • Abnormalities of muscle fibers in maple syrup urine disease.

    abstract::Muscle fiber abnormalities are described in three cases of neonatal maple syrup disease. There were important variations in fiber diameters. Lesions consisted in focal or diffuse destruction of myofibrils. In view of recent biochemical and clinical data, a direct relation between elevated branched-chain amino acid lev...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Ferrière G,de Castro M,Rodriguez J

    更新日期:1984-01-01 00:00:00

  • Nerve cell loss in the thalamic mediodorsal nucleus in Huntington's disease.

    abstract::We estimated the total neurone number, glial number, and glial index (ratio glial cells/neurone) in the thalamic mediodorsal nucleus (MD) in seven patients suffering from Huntington's disease (HD; four males, three females, mean age 52.4 +/- 13.6 years) and age- and sex-matched controls (four males, three females, mea...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Heinsen H,Rüb U,Bauer M,Ulmar G,Bethke B,Schüler M,Böcker F,Eisenmenger W,Götz M,Korr H,Schmitz C

    更新日期:1999-06-01 00:00:00

  • Formation of oedema in transected rat sciatic nerve. A microgravimetric study.

    abstract::The formation of oedema in peripheral nerves was studied in rats at intervals varying from 6 h to 14 days after transection of the right sciatic nerve. Samples were removed proximal and distal to the injury, and the degree of oedema was determined by a microgravimetric method and by measurements of the water content a...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Pettersson CA,Tengvar C

    更新日期:1986-01-01 00:00:00

  • Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer's disease patients.

    abstract::Alzheimer's disease (AD) is a major cause of dementia. Characteristic neuropathological features of AD include neurofibrillary tangles, senile plaques, amyloid angiopathy and microvascular atrophy. The ultra-structure of the microvascular atrophy in AD and its pathogenetic significance have not been defined. This repo...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Claudio L

    更新日期:1996-01-01 00:00:00

  • A monoclonal antibody that recognizes a phosphorylated epitope in Alzheimer neurofibrillary tangles, neurofilaments and tau proteins immunostains granulovacuolar degeneration.

    abstract::A monoclonal antibody, raised against extracts from Alzheimer brain, that recognizes a phosphorylated epitope in high molecular weight neurofilament proteins and tau proteins also immunostains Alzheimer neurofibrillary tangles, neurites in senile plaques and granulovacuolar degeneration. This result suggest that granu...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章


    authors: Dickson DW,Ksiezak-Reding H,Davies P,Yen SH

    更新日期:1987-01-01 00:00:00