Cerebrospinal fluid TAU protein and amyloid β42 in mild cognitive impairment: Prediction of progression to Alzheimer's disease and correlation with the neuropsychological examination

The Neurology Department Memory Clinic and Neurochemistry Laboratory, Saint Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.
Neurocase (Impact Factor: 1.12). 03/2005; 11(1):32-9. DOI: 10.1080/13554790490896901
Source: PubMed


Cerebrospinal fluid (CSF) TAU protein and Amyloid beta42 were able to distinguish between 28 mild cognitive impairment (MCI) patients and both 38 normal aged and 17 anxious and depressed elderly patients, with good sensitivity/specificity when the two measures were combined. These biological markers are independent predictors of the presence of Alzheimer disease (AD), in addition to memory performance. Low Amyloid beta42 level was predictor of a fast progression of MCI patients to full blown dementia. The TAU protein level tended to correlate with memory performance, presumably in relation with the extent of the bilateral medio-temporal damage in early AD.

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    • "Previous research highlights the relevance of utilizing cognitive and CSF markers for early AD detection; however, knowledge regarding the relationship between CSF biomarkers and cognition remains incomplete. Most studies on this topic have revealed either no or weak correlations between cognitive function and amyloid markers (including Aβ 42 ), whereas high correlations were found between cognition and t-tau (Bendlin et al., 2012;Desikan et al., 2012;Glodzik et al., 2011;Ivanoiu and Sindic, 2005;Jack et al., 2008Jack et al., , 2009Jack et al., , 2010Jack et al., , 2013). A previously reported dynamic model of AD biomarkers (Jack et al., 2013Jack et al., , 2010) suggests that the above differences may be attributed to differences in the progression of the involved pathologies. "
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    ABSTRACT: Memory and executive deficits are important cognitive markers of Alzheimer's disease (AD). Moreover, in the past decade, cerebrospinal fluid (CSF) biomarkers have been increasingly utilized in clinical practice. Both cognitive and CSF markers can be used to differentiate between AD patients and healthy seniors with high diagnostic accuracy. However, the extent to which performance on specific mnemonic or executive tasks enables reliable estimations of the concentrations of different CSF markers and their ratios remains unclear.
    No preview · Article · Nov 2015 · Experimental gerontology
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    • "Possibly, a significant correlation between tau protein and neuropsychological scores can be proven only in later stages of the disease. There may be yet another reason why we did not find a correlation between neuropsychological test performance and CSF tau protein, in contrast to previous studies [19] [20] [21]. The increase of tau in the CSF might be much slower than the decrease of Aβ 1−42 , continuing longer into later stages of the disease. "
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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.
    Full-text · Article · Jan 2010 · Journal of Alzheimer's disease: JAD
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    • "Nevertheless, another study did not find any correlations between APOE status and CSF Ttau levels (Maruyama et al. 2001). Another study showed that CSF T-tau levels were negatively correlated with the performance on memory tests (Ivanoiu and Sindic 2005). "
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    ABSTRACT: Diagnosis of mild cognitive impairment (MCI) and its subtypes requires a detailed diagnostic assessment and so may be missed at routine primary-care appointments, since the ordinary dementia screening tests lack sensitivity owing to ceiling effects, especially in highly educated subjects. The study was undertaken using a cross-sectional assessment of 112 elderly subjects (mean age 67.96+/-5.77 years, and mean education level of 12.8+/-5.7 years) with a semi-structured interview and a neuropsychological battery. MCI patients did not differ from controls on total MMSE scores (p=0.212). Nevertheless, MCI patients showed worse performance than controls on the verbal memory task (p=0.012), and "drawing a pentagon" (p=0.03). Amnestic MCI patients performed worse only on the "three-word recall" task (p=0.013); non-amnestic MCI patients performed worse on the "three-stage command" task (p=0.001); and multiple-domain MCI patients performed worse on the "drawing a pentagon" task (p=0.001) and had a trend toward performing poorly on the 'three word recall' task (p=0.06). The analysis of MMSE subtest scores, in addition to MMSE total scores, may increase the sensitivity of the MMSE test in screening for MCI and its subtypes.
    Full-text · Article · Sep 2007 · International Psychogeriatrics
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