Tau and Aβ42 protein in CSF of patients with frontotemporal degeneration

Riemenschneider, Matthias; Wagenpfeil, Stefan; Diehl, J.; Lautenschlager, Nicola T.; Theml, Tina; Heldmann, Barbara; Drzezga, Alexander; Jähn, Thomas; Förstl, Hans; Kurz, Alexander

doi:10.1212/wnl.58.11.1622

Cited by 159 publications

(135 citation statements)

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“…Results on the performance of these biomarkers for differential diagnosis of FTD and AD have been inconsistent. 30,31,32 However, the pattern of mildly increased tau and moderately decreased Ab 1-42 is not unique for FTD, and it can be assumed that the diagnostic value of these biomarkers to discriminate FTD among dementias other than AD is limited. 33 A disease-specific biomarker test for FTD among dementias other than AD and differential diagnostic non-dementive disorders, such as depressive patients with cognitive complaints, has not yet been established.…”

Section: 524mentioning

confidence: 99%

“…This phenomenon has recently contributed to a putative binding protein that masks its epitopes to antibodies during immunologic detection. 4,8,32 Given that similar mechanisms may apply to CSF Ab1-38, the postulated carrier may possess a disease-specific affinity to Ab1-38 in FTD. However, the analogy between the characteristics of the reduction of Ab1-42 and Ab1-38 in AD and FTD, respectively, points to similar diseasespecific mechanisms causing this phenomenon.…”

Section: 524mentioning

confidence: 99%

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Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias

et al. 2007

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Biomarkers for differential diagnosis of the three most frequent degenerative forms of dementia, Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementias (FTD), are currently under intensive investigation, but disease-specific biomarkers for FTD and DLB are still lacking. We analyzed 303 cerebrospinal fluid (CSF) samples of 71 AD, 32 DLB and 36 FTD patients in comparison to 93 various other dementias (OD), 20 peripheral neurologic disease (PND) controls, 25 neurodegenerative disorders without dementia (ND) and 26 depressive cognitive complainers (DCC) for distinct CSF amyloid-b (Ab) peptide patterns, using the quantitative Ab-SDS-PAGE/immunoblot. Additionally, the novel electrochemiluminescence technique (MSD) was used to validate the measures on Ab1-38. The main outcome measures were a striking decrease of Ab1-42 in AD (P = 7.4 Â 10 À19 ), and most interestingly a pronounced decrease of Ab1-38 in FTD (P = 9.6 Â 10 À7 ). Moreover, a novel peptide that most probably represents an oxidized a-helical form of Ab1-40 (Ab1-40 ox ) displayed a highly significant increase in DLB (P = 3.7 Â 10 À3) as compared to non-demented disease controls. The overall diagnostic accuracy of percentage Ab peptide abundances (Ab1-X%) was clearly superior to absolute CSF Ab levels. Ab1-42% and Ab1-38% enabled contrasts of 85% or beyond to distinguish AD and FTD, respectively, from all other investigated subjects. Ab1-40 ox % yielded a diagnostic sensitivity and specificity of 88 and 73% for the detection of DLB among all other investigated patients. We found a strong correlation between Ab1-38 levels as measured by the Ab-SDS-PAGE/immunoblot and MSD, respectively. CSF Ab peptides may reflect disease-specific impact of distinct neurodegenerative processes on Ab peptide metabolism and represent a potential diagnostic biomarker for AD, FTD and DLB.

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Section: 524mentioning

confidence: 99%

Section: 524mentioning

confidence: 99%

Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias

et al. 2007

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“…61 The 20 largest studies 14,20,24,41,50,56,[62][63][64][65][66][67][68][69][70][71][72][73][74][75] including more than 2000 AD patients and 1000 controls, evaluating the most commonly used ELISA method for T-tau in CSF, 14 are summarized in Table 2. The mean sensitivity to discriminate AD from nondemented aged individuals has been 81%, at a specificity level of 91% (Table 2).…”

Section: Csf T-taumentioning

confidence: 99%

“…A mild to moderate decrease in CSF A␤42 is found in a percentage of patients with FTD and VAD. 50,52,67,72 …”

Section: A␤42mentioning

confidence: 99%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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“…The more recent longitudinal studies use the combination of high tau and low Aβ42 to correlate their levels to the stage of the disease 13,15 . Since amyloid deposition is not exclusive of AD brains, occurring in normal aging and also in other neurological diseases, additional investigation have shown a decrease in Aβ CSF levels in other conditions such as Creutzfeldt-Jakob disease (CJD) 16 , some cases of frontotemporal dementia (FTD) and vascular dementia (VD) 17 . In 1993, Vandermeeren et al 18 developed an immunoassay able to detect tau protein in CSF and subsequent studies concluded that its levels were significantly higher in AD patients when compared to other neurological diseases and normal controls even in the early stages of the disease 4,10 .…”

mentioning

confidence: 99%

Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with Alzheimer's disease and other dementias: preliminary findings

Hartmann

Almeida²,

Livramento

et al. 2004

Arq. Neuro-Psiquiatr.

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-Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and tau-associated neurofibrillary tangles in the cerebral tissue. The search for antemortem biomarkers is intense including analysis of cerebrospinal fluid (CSF) β-amyloid and tau proteins concentrations seeking for an accurate and early diagnosis. Levels of hyperphosphorylated tau at threonine 181 were measured in the CSF of 34 patients with AD (19 with senile AD -SAD and eight with presenile AD -PSAD) and seven with other dementias (OD). The levels of CSF phosphotau were significantly higher in the AD patients compared to OD (AUC 0.812), with no association with severity of dementia, age of onset, duration of the disease or scores in the Mini-Mental State Examination. There were no differences of phosphotau levels between SAD and PSAD patients. These findings corroborate some previous studies and indicate that CSF phosphotau may help to differentiate AD from other dementias.KEY WORDS: Alzheimer's disease, differential diagnosis, cerebrospinal fluid, tau protein. Proteína tau hiperfosforilada no líquido cefalorrraqueano de pacientes com doença de Alzheimer e outras demências: resultados preliminaresRESUMO -A doença de Alzheimer (DA) se caracteriza pelo achado anátomo-patológico de acúmulo de placas senis e emaranhados neurofibrilares associados à proteína tau no tecido cerebral. A pesquisa por marcadores biológicos antemortem está focada nas concentrações das proteínas β-amilóide e tau no líqui-do cefalorraqueano (LCR) objetivando um diagnóstico mais precoce e acurado da doença. Os níveis de proteína tau hiperfosforilada no sítio 181 foram determinados no LCR de 34 pacientes com DA (19 com DA senil -DAS e oito com DA pré-senil -DAPS) e sete pacientes com outras demências (OD). Os níveis de fosfotau foram significativamente mais elevados em pacientes com DA quando comparados com OD (AUC 0,812), sem relação com gravidade da demência, idade de início, duração da doença e escores do MiniExame do Estado Mental. Não foram observadas diferenças entre os níveis de fosfotau em pacientes com DAS e DAPS. Estes achados corroboram os dados encontrados em estudos prévios e indicam que o nível de fosfotau no LCR dos pacientes pode colaborar na diferenciação da DA com outras demências. PALAVRAS-CHAVE: doença de Alzheimer, diagnóstico diferencial, líquido cefalorraqueano, proteína tau.Alzheimer's disease (AD) is the main cause of dementia in Western countries, being responsible for more than 50% of the cases 1 . The clinical diagnosis of AD is characterized by an exclusionary process. The definite diagnosis is possible only on neuropathological examination, by the observation of the senile plaques and the neurofibrillary tangles (NFTs) in the cerebral tissue 2 . The NFTs are intraneuronal cytoplasmatic structures composed by paired helical filaments (PHFs) of hyperphosphorylated form of the microtubule-associated protein tau. In AD, these NFTs are localized preferentially in pyramidal cells of the hippocampus and entorhina...

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Tau and Aβ42 protein in CSF of patients with frontotemporal degeneration

Abstract: In FTD, CSF levels of tau are elevated and Abeta42 levels are decreased. With use of these markers, subjects with FTD can be distinguished from control subjects and from patients with AD with reasonable accuracy.

Cited by 159 publications

References 39 publications

Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias

Validation of amyloid-β peptides in CSF diagnosis of neurodegenerative dementias

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with Alzheimer's disease and other dementias: preliminary findings

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