Evaluation of CSF-tau and CSF-Aβ42 as Diagnostic Markers for Alzheimer Disease in Clinical Practice

Andreasen, Niels; Minthon, Lennart; Davidsson, Pia; Vanmechelen, Eugeen; Vanderstichele, Hugo; Winblad, Bengt; Blennow, Kaj

doi:10.1001/archneur.58.3.373

Cited by 520 publications

(426 citation statements)

References 36 publications

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“…An expert review recently considered it adequate for applicable Alzheimer's disease diagnostic testing in addition to clinical criteria (Andreasen et al ., 2003). Decreased Aβ1–42 levels have also been reported for DLB (Andreasen et al ., 2001; Mollenhauer et al ., 2005) and PDD (Mollenhauer et al ., 2005) patients. Thus, the specificity of this finding and consequently its differential diagnostic value in distinguishing between different subtypes of dementias was low (Andreasen et al ., 2001, 2003; Mollenhauer et al ., 2005).…”

Section: Introductionsupporting

confidence: 54%

“…87% sensitivity and specificity each) could be obtained. The previously reported sensitivities for Alzheimer's disease detection and specificities for DLB exclusion, respectively, did not exceed 75% in a combined assay of tau and Aβ 1–42 enzyme-linked immunosorbent assay (ELISA) (Andreasen et al ., 2001). Thus, the actual differential diagnostic value of Aβ peptide patterns can be considered to be as relevant as the established ELISAs for tau and Aβ1–42.…”

Section: Discussionmentioning

confidence: 98%

“…Decreased levels of CSF Aβ1–42 have been reported for patients with Alzheimer's disease (Motter et al ., 1995; Andreasen et al ., 2001, 2003; Wiltfang et al ., 2002, 2003; Mollenhauer et al ., 2005) and DLB (Andreasen et al ., 2001; Mollenhauer et al ., 2005). The reduction of Aβ1–42 levels in Alzheimer's disease has been explained by an increased clearance of the peptide from CSF into senile amyloid plaques for a long time (Motter et al ., 1995).…”

Section: Discussionmentioning

confidence: 99%

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CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

Bibl¹,

Mollenhauer²,

Esselmann³

et al. 2006

Brain

191

146

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As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Aβ) peptides, such as Aβ1–42. Absolute Aβ1–42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Aβ-sodium-dodecylsulphate–polyacrylamide-gel-electrophoresis with Western immunoblot (Aβ-SDS–PAGE/immunoblot) revealed a highly conserved Aβ peptide pattern of the carboxy-terminally truncated Aβ peptides 1–37, 1–38, 1–39 in addition to 1–40 and 1–42 in human CSF. We used the Aβ-SDS–PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Aβ peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Aβ peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases—Alzheimer's disease, DLB and PDD. The Aβ peptide patterns displayed disease-specific variations and the ratio of the differentially altered Aβ1–42 to the Aβ1–37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Aβ-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized α-helical form of Aβ1–40 (Aβ1–40*). The increased abundance of Aβ1–40* probably reflects a disease-specific alteration of the Aβ1–40 metabolism in DLB. We conclude that Aβ peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Aβ peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

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Section: Introductionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

Bibl¹,

Mollenhauer²,

Esselmann³

et al. 2006

Brain

191

146

View full text Add to dashboard Cite

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“…While it is clear that A42 along with tau protein levels in CSF are useful in clinical routine (Andreasen et al, 2001;Frisoni et al, 2009) and probably also to detect biochemical effects on amyloid deposition and axonal degeneration of novel drug candidates against AD (Bateman et al, 2009;Kadir et al, 2008;Lannfelt et al, 2008), it has been difficult to find reliable amyloid biomarkers in peripheral blood (Irizarry, 2004;Zetterberg, 2008). Many studies have examined plasma levels of A in the context of sporadic AD but the findings are contradictory.…”

Section: A-related Proteins As Core Neurochemical Markers Of Admentioning

confidence: 99%

Amyloid β and APP as biomarkers for Alzheimer’s disease

Zetterberg

Blennow

Hanse

2010

Experimental Gerontology

Self Cite

109

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“…Andreasen et al (2001) também obtiveram estimativas semelhantes, com valores preditivos positivo e negativo de 90% e 95%, respectivamente, numa prevalência de DA provável de 44%. Para avaliar dados de análise simultânea de Aβ1-42 e tau no LCR, Galasko et al (1998) utilizaram o sistema de classificação binário, obtendo 85,2% de diagnósticos corretos, com sensibilidade e especificidade de 90% e 80% respectivamente.…”

Section: Análise Combinada De Parâmetros Do Lcrunclassified

Trabalho de consenso de força-tarefa da WFSBP sobre marcadores biológicos das demências: contribuição da análise do LCR e do sangue para o diagnóstico precoce e diferencial das demências

Wiltfang¹,

Lewczuk²,

Riederer³

et al. 2009

Rev. psiquiatr. clín.

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RevisãoTrabalho de consenso de força-tarefa da WFSBP # sobre marcadores biológicos das demências: Contribuição da análise do LCR e do sangue para o diagnóstico precoce e diferencial das demências ResumoO envelhecimento da população e o aumento da expectativa de vida resultam em um número cada vez maior de pacientes com demência. Os déficits cognitivos podem ser manifestações de uma doença curável do sistema nervoso central (por exemplo, neuroinflamação), como também de uma doença atualmente considerada irreversível, como a doença de Alzheimer (DA). Tendo em vista as novas abordagens terapêuticas para a DA, em que se avalia o potencial modificador da patogenia, torna-se necessário o estabelecimento de um diagnóstico confiável em vida. Embora a análise do líquido cefalorraquidiano (LCR) e do soro seja realização de rotina em doenças neuroinflamatórias, ainda necessita de padronização para ser usada como instrumento auxiliar no diagnóstico clínico da DA. Vários parâmetros relacionados à DA (tau total, formas fosforiladas de tau, peptídeos Aβ, genótipo ApoE, p97 etc.) podem ser determinados no LCR. A combinação de alguns desses parâmetros proporciona sensibilidade e especificidade na faixa de 85% para o diagnóstico da DA, um valor usualmente atribuído a um bom instrumento de diagnóstico. Nesta revisão, são discutidas as publicações mais recentes sobre os marcadores neuroquímicos para o diagnóstico clínico das demências, com ênfase no diagnóstico precoce e diferencial da DA. Discutem-se brevemente as novas perspectivas oferecidas por tecnologias recentes, tais como a FCS (fluorescence correlation spectroscopy) e a técnica de espectrometria de massa pelo método SELDI-TOF (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). Wiltfang J, et al. / Rev Psiq Clín. 2009;36( Wiltfang J, et al. / Rev Psiq Clín. 2009;36(1):1-16 IntroduçãoEm função do envelhecimento populacional e do aumento da expectativa de vida, os transtornos demenciantes irão se tornar um sério problema para os sistemas de atendimento à saúde. Em relação à doença de Alzheimer (DA), apesar do número cada vez maior de pacientes, poucos progressos foram feitos em direção a um melhor padrão para o diagnóstico em vida. Embora a sensibilidade do diagnóstico clínico seja relativamente alta (93%), a especificidade pode ser mais baixa -55%, conforme relatado por um estudo clínico-patológico multicêntrico (Mayeux, 1998). Em mãos experientes, o diagnóstico clínico de DA pode ser preditivo da confirmação neuropatológica em 80% a 90% dos casos; contudo, o diagnóstico da DA em fases iniciais assim como o diagnóstico diferencial das apresentações demenciais incomuns continuam a ser tarefas difíceis em bases puramente clínicas. A introdução das drogas antidemência, tais como os inibidores da acetilcolinesterase para o tratamento da DA, representou um potencial de benefício terapêutico considerável, ante uma doença até então considerada irreversível (recente revisão de Bullock, 2002;Knopman, 2001). Desse modo, a necessidade de se estabelec...

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Evaluation of CSF-tau and CSF-Aβ42 as Diagnostic Markers for Alzheimer Disease in Clinical Practice

Cited by 520 publications

References 36 publications

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

CSF amyloid-β-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia

Amyloid β and APP as biomarkers for Alzheimer’s disease

Trabalho de consenso de força-tarefa da WFSBP sobre marcadores biológicos das demências: contribuição da análise do LCR e do sangue para o diagnóstico precoce e diferencial das demências

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