Total tau protein, phosphorylated tau (181p) protein, β-amyloid1–42, and β-amyloid1–40 in cerebrospinal fluid of patients with dementia with Lewy bodies

Abstract

The intra vitam diagnosis of different dementias is still based on clinical grounds. So far, no technical investigations have been available to support these diagnoses. For tau protein and beta-amyloid(1-42) in cerebrospinal fluid (CSF), promising results for the diagnosis of Alzheimer's disease (AD) have been reported; however, their differential diagnostic spectrum is limited, as was recently shown for dementia with Lewy bodies (DLB) and for AD. Therefore, further marker proteins have to be established to ameliorate, support, and differentiate these clinical diagnoses. We evaluated beta-amyloid(1-40) and phosphorylated tau protein (181p), in addition to total tau protein and beta-amyloid(1-42), in 20 patients with DLB, 34 AD patients, and 20 non-demented neurological controls (NDCs). All markers could differentiate between the dementia groups (AD, DLB) and the controls. AD and DLB could be differentiated only by levels of total tau protein and by the ratio total tau protein/phosphorylated tau protein. However, values still overlapped markedly. In some cases, tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited, especially because of mixed pathology. We conclude that more specific markers have to be established to differentiate between these diseases.

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

“…Therefore, the earliest phase of AD neuropsychological testing should be focused on learning tests and on recall of learned information after a delay or following interfering materials [7,15,16]. But the few studies, that have been published up to now on the correlation between CSF markers and cognitive decline, often relied on cognitive tests that are rather insufficient for this purpose, like the Mini Mental Status Examination (MMSE) [17][18][19][20]. This instrument yields a composite score of cognitive impairment and is rather insensitive to mild impairment.…”

Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications

“…Ideally, an internal peptide standard corresponds to a peptide synthetized with the incorporation of stable isotopes such as 13 C or 15 N. These results in a known mass increment, explaining the term often used of "heavy" standard [68]. To quantify Aβ peptides via LC-MS/MS, the ratio between the MS signal intensity of the endogenous peptide and that of its heavy counterpart present at a known concentration, is generally measured in samples and a set of calibrators [69].…”

“…The diagnosis of AD is based on neuropsychological tests, functional and morphologic imaging (MRI, hippocampal volumetry), and the levels of the following biomarkers present in the CSF: Aβ peptides, tau and p-tau(181) proteins [10][11][12][13]. These biomarkers which are now routinely measured in specialized laboratories [12,14] are useful to predict and diagnose AD.…”

“…These biomarkers which are now routinely measured in specialized laboratories [12,14] are useful to predict and diagnose AD. In practice, two Aβ peptides (Aβ 1-40 and Aβ 1-42) are quantified by enzyme-linked immuno-sorbent assay (ELISA) [13,14]. This quantification is based the recognition of the epitopes corresponding to the C-terminus amino acids of Aβ 1-40 and Aβ 1-42 using, respectively, the 2G3 and 21F12 antibodies.…”

Disclosure of Alzheimer’s Disease Biomarker Status in Subjects with Mild Cognitive Impairment

“…Conflicting injury markers may indicate variability in disease expression [9]. Abnormal amyloid markers with normal injury markers may reflect early-stage AD or non-AD causes of MCI such as Lewy body dementia [18]. Abnormal injury markers with normal amyloid markers may suggest non-AD causes of MCI or an atypical presentation of AD.…”