Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
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Cites background from "Cerebrospinal fluid biomarker signa..."
...Markers of tau accumulation include CSF measures of increased total tau or phosphorylated-tau (p-tau) [14–16]....
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...Markers of Aβ deposition include both cerebrospinal fluid (CSF) measures of lower Aβ42 levels [14–16] and positron-emission tomography (PET) evidence of Aβ deposition, using a variety of specific ligands [17]....
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5,671 citations
Cites background from "Cerebrospinal fluid biomarker signa..."
...In particular, there is an important need to evaluate methods for determining “amyloid-positivity” because it remains unclear whether there is a biologically relevant continuum of Ab accumulation, or whether there is a clear threshold or “cut-off” value that could be defined on the basis of predictive value for subsequent clinical decline, as has been suggested in several CSF studies [28,66]....
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...Although recent work suggests there may be a CSF Ab42 cutoff value that is predictive of progression from MCI to AD dementia [66], it is unknown whether a similar threshold will be optimal in prediction of decline in individuals with normal or near normal cognition....
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References
1,641 citations
"Cerebrospinal fluid biomarker signa..." refers result in this paper
...Ann Neurol 2009;65:403–413 If the clinical diagnosis of probable AD is imprecise with accuracy rates of approximately 90% or lower using established consensus criteria for probable AD, but definite AD requires autopsy confirmation, it is not surprising that diagnostic accuracy is lower at early and presymptomatic stages of AD.1–4 It is believed that the development of full-blown AD takes place over an approximately 20-year prodromal period, but this is difficult to determine in the absence of biomarkers that reliably signal the onset of nascent disease before the emergence of measurable cognitive impairments....
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...Interpretation: The CSF biomarker signature of AD defined by A 1-42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD....
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...The combination of increased CSF concentrations of t-tau and phosphotau (p-tau) species and decreased concentrations of A 1-42 are considered to be a pathological CSF biomarker signature that is diagnostic for AD.5,6,8,9 Notably, recent studies have provided compelling preliminary data to suggest that this combination of CSF tau and A biomarker changes may predict the conversion to AD in mild cognitive impairment (MCI) subjects.10 Thus, an increase in levels of CSF tau associated with a decline in levels of CSF A 1-42 may herald the onset of AD before it becomes clinically manifest....
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...An AD-like pathological CSF profile for A 1-42 and t-tau, the t-tau/A 1-42 ratio, was detected in 33 of the 37 ADNI MCI subjects who converted to a diagnosis of probable AD 1 year after their baseline CSF collection, whereas the addition of APO 4 as a covariate in the LR model did not improve on the prediction of conversion from MCI to probable AD....
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...These data confirm the findings of the majority of single and smaller multicenter studies for these biomarkers in AD subjects wherein most investigators report increases in t-tau, p-tau181p concentrations, t-tau/A 1-42, and p-tau181p/A 1-42 ratio values when comparing NC with MCI, and then further increases in these values when comparing MCI with AD.7–10,12–16 A 1-42 average concentrations, on the other hand, decrease when comparing NC with MCI, then decrease further in comparing MCI with AD.7– 10,12–16 Closer examination of the distribution of each biomarker and ratios demonstrated that the distributions are not normal, and for A 1-42, the distributions appear to be bimodal (Fig 1)....
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1,222 citations
"Cerebrospinal fluid biomarker signa..." refers background in this paper
...Ann Neurol 2009;65:403–413 If the clinical diagnosis of probable AD is imprecise with accuracy rates of approximately 90% or lower using established consensus criteria for probable AD, but definite AD requires autopsy confirmation, it is not surprising that diagnostic accuracy is lower at early and presymptomatic stages of AD.1–4 It is believed that the development of full-blown AD takes place over an approximately 20-year prodromal period, but this is difficult to determine in the absence of biomarkers that reliably signal the onset of nascent disease before the emergence of measurable cognitive impairments....
[...]
...Interpretation: The CSF biomarker signature of AD defined by A 1-42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD....
[...]
...The combination of increased CSF concentrations of t-tau and phosphotau (p-tau) species and decreased concentrations of A 1-42 are considered to be a pathological CSF biomarker signature that is diagnostic for AD.5,6,8,9 Notably, recent studies have provided compelling preliminary data to suggest that this combination of CSF tau and A biomarker changes may predict the conversion to AD in mild cognitive impairment (MCI) subjects.10 Thus, an increase in levels of CSF tau associated with a decline in levels of CSF A 1-42 may herald the onset of AD before it becomes clinically manifest....
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...An AD-like pathological CSF profile for A 1-42 and t-tau, the t-tau/A 1-42 ratio, was detected in 33 of the 37 ADNI MCI subjects who converted to a diagnosis of probable AD 1 year after their baseline CSF collection, whereas the addition of APO 4 as a covariate in the LR model did not improve on the prediction of conversion from MCI to probable AD....
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...The combination of increased CSF concentrations of t-tau and phosphotau (p-tau) species and decreased concentrations of A 1-42 are considered to be a pathological CSF biomarker signature that is diagnostic for AD.(5,6,8,9) Notably, recent studies have provided compelling preliminary data to suggest that this combination of CSF tau and A biomarker changes may predict the conversion to AD in mild cognitive impairment (MCI) subjects....
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992 citations
"Cerebrospinal fluid biomarker signa..." refers methods in this paper
...Discussion ADNI is a multisite, prospective clinical study funded by the National Institute on Aging, industry, and foundations (see Acknowledgements for details on sources for ADNI funding) with the following mission: (1) to develop standardized neuroimaging and biomarker methods for AD clinical trials; (2) to determine optimum methods for acquiring and processing brain images; (3) to validate AD neuroimaging and biomarker findings by correlating them with ADNI behavioral test data; and (4) to provide a database available to the public for all ADNI findings for further analysis.(7,11) This is the first report on studies of baseline CSF samples from ADNI subjects, and we measured tau and A 1-42 values in the approximately 50% of ADNI subjects who consented to lumbar puncture, including representatives of the AD, MCI, and NC groups....
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860 citations
852 citations