Anomalously phosphorylated tau and Aβ fragments in the CSF correlates with cognitive impairment in MCI subjects

Maccioni, Ricardo B.; Lavados, Manuel; Guillón, Marta; Mujica, Cristina; Bosch, Ruben van den; Farías, Gustavo; Fuentes, Patricio

doi:10.1016/j.neurobiolaging.2005.01.011

Cited by 62 publications

(33 citation statements)

References 44 publications

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“…In the current study, we have verified that a significant pathological consequence of ADDL binding to CNS neurons is tau hyperphosphorylation. ADDL-induced tau hyperphosphorylation was found at epitopes characteristically phosphorylated in AD, namely Ser404, Thr231, Thr 181, Ser 202 and Thr 205 [18,19,40]. Importantly, we show that tau hyperphosphorylation is induced not only by synthetic ADDLs, but also by soluble extracts containing ADDLs obtained from AD brains.…”

Section: Discussionmentioning

confidence: 54%

“…Our first experiments examined the effects of Aβ oligomers on tau phosphorylation in B103 neuroblastoma cells using AT8, an antibody that recognizes tau phosphorylated at residues Ser 202 and Thr 205 and has been shown to detect abnormal hyperphosphorylated tau in cerebrospinal fluid from AD patients [40]. While vehicle-treated cells ( Fig.…”

Section: Addls Induce Tau Hyperphosphorylation In B103 Neuroblastoma mentioning

confidence: 99%

See 1 more Smart Citation

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

Felice

Lambert

et al. 2008

Neurobiology of Aging

397

315

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Alzheimer's disease (AD) is characterized by presence of extracellular fibrillar Aβ in amyloid plaques, intraneuronal neurofibrillary tangles consisting of aggregated hyperphosphorylated tau and elevated brain levels of soluble Aβ oligomers (ADDLs). A major question is how these disparate facets of AD pathology are mechanistically related. Here we show that, independent of the presence of fibrils, ADDLs stimulate tau phosphorylation in mature cultures of hippocampal neurons and in neuroblastoma cells at epitopes characteristically hyperphosphorylated in AD. A monoclonal antibody that targets ADDLs blocked their attachment to synaptic binding sites and prevented tau hyperphosphorylation. Tau phosphorylation was blocked by the Src family tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-D)pyramide (PP1), and by the phosphatidylinositol-3-kinase inhibitor LY294002. Significantly, tau hyperphosphorylation was also induced by a soluble aqueous extract containing Aβ oligomers from AD brains, but not by an extract from non-AD brains. Aβ oligomers have been increasingly implicated as the main neurotoxins in AD, and the current results provide a unifying mechanism in which oligomer activity is directly linked to tau hyperphosphorylation in AD pathology.

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Section: Discussionmentioning

confidence: 54%

Section: Addls Induce Tau Hyperphosphorylation In B103 Neuroblastoma mentioning

confidence: 99%

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

Felice

Lambert

et al. 2008

Neurobiology of Aging

397

315

View full text Add to dashboard Cite

show abstract

“…Ivanoiu & Sindic [21] and Stomrud et al [17] reported that a low level of Aβ predicts cognitive decline in MCI patients. Maccioni and coworkers [43] showed that Aβ 1−42 level correlates with cognitive performance in MCI patients after dividing the patient group in different degrees of impairment. In a recent study of Forsberg et al [44], which only involved memory testing and no other cognitive tests, a correlation was found between Aβ 1−42 level and memory performance in the MCI patients, but not in the AD patients.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Cognitive Impairment and CSF Biomarkers in Amnesic MCI, non-Amnesic MCI, and Alzheimer's Disease

Haldenwanger

Eling

Kastrup

et al. 2010

JAD

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Abstract. Decreased delayed recall, decreased amyloid-β peptides (Aβ1−42), and increased tau protein concentration in cerebrospinal fluid (CSF) are generally regarded to be valid neuropsychological and biological markers for Alzheimer's disease (AD). Previous studies failed to demonstrate clear-cut correlations between neuropsychological impairment and CSF markers. In this study we test recent models of disease progression, that propose that changes in CSF biomarkers already reach a plateau in a preclinical phase, before cognitive decline begins, that is, even before MCI can be diagnosed. We recruited 73 patients with probable AD (n = 36) and mild cognitive impairment (MCI) (amnesic MCI = 25; non-amnesic MCI = 12). We used the CERAD-NP, a widely used neuropsychological battery with norms for different age and education groups, and additional neuropsychological tests for assessing the cognitive profile of these patient groups. We found a significant correlation between Aβ1−42 in the CSF and memory performance for amnesic MCI patients, but not for non-amnesic MCI and AD patients. All other correlations between cognitive tasks and Aβ1−42 were not significant. Tau protein concentration in the CSF was not correlated with any neuropsychological marker in any of the patients groups. We conclude that the decrease of Aβ1−42 in the CSF mirrors disease progression during the early stages up into AD and therefore is not restricted to the preclinical phase. The decrease of Aβ1−42 reaches a plateau only in the full blown demented syndrome and further functional disease progression is then related to neurodegeneration without further reduction of Aβ1−42 in the CSF.

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“…So, an increase in P-tau CSF levels is observed in AD and MCI patients (Itoh, Arai et al 2001;Andreasen, Vanmechelen et al 2003;Herukka, Hallikainen et al 2005). Moreover, cognitive decline is correlated with CSF increasing levels of P-tau, these CSF tau species might specifically mark a cerebral degenerative process (Maccioni, Lavados et al 2006;Wallin, Blennow et al 2006). While other P-tau species have been measured, only CSF levels of tau proteins phosphorylated at serine 181 (P-tau 181 ) or threonine 231 (P-tau 231 ) seem to clearly improve the accuracy of the diagnostic of AD (Buerger, Zinkowski et al 2002;Hampel and Teipel 2004;Mitchell 2009).…”

Section: Which Csf Biochemical Markers Might Allow Us To Detect Alzhementioning

confidence: 96%

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Elmoualij¹,

Dupiereux-Fettweis²,

Seguin³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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Anomalously phosphorylated tau and Aβ fragments in the CSF correlates with cognitive impairment in MCI subjects

Cited by 62 publications

References 44 publications

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

Correlation between Cognitive Impairment and CSF Biomarkers in Amnesic MCI, non-Amnesic MCI, and Alzheimer's Disease

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

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