Value of CSF β-amyloid1–42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment

Abstract

Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) bamyloid 1-42 (Ab 1-42 ) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Ab 1-42 and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Ab 1-42 and CSF tau. The levels of CSF tau were increased, whereas levels of Ab 1-42 were decreased in MCI subjects. Ab 1-42 predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Ab 1-42 , but not other predictor variables (tau protein, gender, age, apolipoprotein E e4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (Po0.05). Our findings support the notion that CSF tau and Ab 1-42 may be useful biomarkers in the early identification of AD in MCI subjects.

Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease

“…The cerebrospinal fluid (CSF) biomarkers tau and β-amyloid 1-42 (Aβ42) can be used to detect preclinical AD in MCI populations with relatively high diagnostic accuracy [4,15,17].…”

Cerebrospinal fluid biomarkers of Alzheimer’s disease

“…CSF p-tau correlates well with cognitive decline and is boosted in AD patients compared with normal controls [57][58][59] .…”

“…CSF t-tau has a sensitivity of 83% and a specifi city of 90% in discriminating AD from healthy controls [58] . Taking into account that CSF tau is also elevated in other neurological disorders, such as Parkinson's disease (PD) and frontotemporal dementia (FTD), it is essential to augment the specifi city of CSF t-tau as a biomarker for AD.…”

“…Tau undergoes abnormal hyperphosphorylation at various sites, such as threonine 181 and 231, and serine 199, 235, 396 and 404 [35] . Due to aberrant phosphorylation, tau is unable to bind and stabilize the microtubules, contributing to neuronal loss [57] .A number of studies found increased levels of CSF t-tau in AD cases relative to controls [47,[56][57][58][59][60][61][62][63][64] . CSF t-tau has a sensitivity of 83% and a specifi city of 90% in discriminating AD from healthy controls [58] .…”

“…CSF t-tau has a sensitivity of 83% and a specifi city of 90% in discriminating AD from healthy controls [58] . Taking into account that CSF tau is also elevated in other neurological disorders, such as Parkinson's disease (PD) and frontotemporal dementia (FTD), it is essential to augment the specifi city of CSF t-tau as a biomarker for AD.CSF p-tau correlates well with cognitive decline and is boosted in AD patients compared with normal controls [57][58][59] .This may be attributed to the release of p-tau from degenerating neurons and subsequent diffusion into the CSF. At the same time, increasing p-tau could disturb the balance of binding between tau and microtubules, leading to higher levels of p-tau in the cytosol.…”