Assessment of cerebrospinal fluid (CSF) beta-amyloid (1–42), phosphorylated tau (ptau-181) and total Tau protein in patients with Alzheimer’s disease (AD) and other dementia at Siriraj Hospital, Thailand
The combination of decreased cerebrospinal fluid (CSF) levels of beta-amyloid (1-42) and increased levels of phosphorylated tau (ptau-181) or total tau protein are known to be biomarkers ofAlzheimer's disease (AD). These biomarkers can also be used as predictors of disease progression in persons with mild cognitive impairment. Utilizing biomarkers to differentiate Alzheimer's disease (AD) against non-Alzheimer dementia (non-AD) needs to be explored.
To evaluate the clinical use ofCSF biomarker: beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein for distinguishing Alzheimer's disease (AD) from non-Alzheimer dementia (non-AD) in Thai patients.
Thirty patients diagnosed of dementia during 2005-2007 at Siriraj hospital were offered CSF analysis for beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein. Diagnosis of dementia was performed by a concensus diagnostic group utilizing a standard criteria for diagnosis of AD and other dementia. All CSF testing was performed by Enzyme-Linked Immunoassay (ELISA) technique of the INNOTESTM to analyze these biomarkers.
Thirty demented patients were recruited in the study. Fourteen had AD and 16 had non-AD including 5 vascular dementia, 5 normal pressure hydrocephalus, 4 frontotemporal lobar degeneration and others. Mean age of the AD group was 67.79 (12.30) and that of non-AD group was 65.75 (15.04). Twelve AD had decreased levels of CSF /3-amyloid (1-42) (less than 487 pg/ml). Only one patient with AD had increased CSF phosphorylated tau (ptau-181) (more than 61 pg/ml). None of theAD patient had increased CSF total tau (more than 425 pg/ml). Eight patients with non-AD had decreased levels of CSF p-amyloid (1-42), one had increased CSF total tau protein, and none had increased CSF phosphorylated tau (ptau-181) protein. The sensitivity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 85.71%. Those of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 7.14% and 0% consecutively. The specificity of decreased level of CSF beta-amyloid (1-42) in AD against non-AD dementia was 50%. The specificity of increased CSF total tau and phosphorylated tau (ptau-181) protein in AD against non-AD dementia were 100% and 93.75% sequentially. The combination of 2 biomarkers would increase specificity but decrease sensitivity.
CSF biomarker analysis should be encouraged to use as diagnostic aid in memory clinic especially to help diagnosis of atypical presentation of AD. The usefulness of longitudinal data needs to be explored.
Available from: Ricardo S Osorio
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ABSTRACT: Late-Life Major Depression (LLMD) is a complex heterogeneous disorder that has multiple pathophysiological mechanisms such as medical comorbidity, vascular-related factors and Alzheimer's disease (AD). There is an association between LLMD and AD, with LLMD possibly being a risk factor for, or early symptom of AD and vascular dementia. Whether depression is an etiologic risk factor for dementia, or part of the dementia prodrome remains controversial. AD has a long prodromal period with the neuropathologic features of the disease preceding the onset of clinical symptoms by as much as 15-20 years. Clinicopathological studies have provided robust support for the importance of Aβ42 in the pathogenesis of AD, but several other risk factors have also been identified. Given the relationship between Aβ42 and AD, a potential relationship between Aβ42 and LLMD would improve the understanding of the association between LLMD and AD. We reviewed 15 studies that analyzed the relationship between soluble Aβ42 and LLMD. For studies looking at plasma and/or cerebrospinal fluid (CSF) levels of Aβ42, the relationship between LLMD and soluble Aβ42 was equivocal, with some studies finding elevated Aβ42 levels associated with LLMD and others finding the opposite, decreased levels of Aβ42 associated with LLMD. It may be that there is poor reliability in the diagnosis of depression in late life, or variability in the criteria and the scales used, or subtypes of depression in late life such as early vs. late onset depression, vascular-related depression, and preclinical/comorbid depression in AD. The different correlations associated with each of these factors would be causing the inconsistent results for soluble Aβ42 levels in LLMD, but it is also possible that these patterns derive from disease stage-dependent differences in the trajectory of CSF Aβ42 during older age, or changes in neuronal activity or the sleep/wake cycle produced by LLMD that influence Aβ42 dynamics.
Available from: PubMed Central
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ABSTRACT: Vascular factors are thought to contribute to the development of disease pathology in neurodegenerative dementia such as Alzheimer's disease (AD). Another entity, called vascular dementia (VaD), comprises a less defined group of dementia patients having various vascular diseases that especially emerge in the elderly population and require valid options for examination and differential diagnosis. In the context of a retrospective study, we analyzed the cerebrospinal fluid (CSF) biomarkers t-tau, p-tau and Aß42 of a total of 131 patients with AD (n = 47), mild cognitive impairment (MCI) (n = 22), VaD (n = 44) and stroke (n = 18). We found a remarkable alteration in CSF biomarker profile in AD, VaD and in acute ischemic events. CSF profile in AD patients was altered in a very similar way as in stroke patients, without statistical differences. In stroke, increase depend largely on size and duration after the initial event. Total tau levels were useful to differ between VaD and stroke. Aß42 decreased in a similar way in AD, VaD and stroke and had a trend to lower levels in MCI but not in controls.
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To assess whether biomarker τ protein could differentiate between Alzheimer's disease (AD) and vascular dementia (VaD).
We conducted a comprehensive search to identify studies on τ protein, patients with AD, and patients with VaD. Cerebrospinal fluid (CSF) τ protein levels were compared to discriminate among patients with AD, healthy controls, and patients with VaD by a meta-analysis.
Patients with AD exhibit significantly higher CSF τ protein levels than healthy controls or patients with VaD in the Chinese population.
Our findings suggested that CSF τ protein levels were found to be significantly associated with AD in the Chinese population. Measurement of τ protein could help in attenuating the strict distinction between AD and VaD.
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