Decreased Amyloid 1-42 and Increased Tau Levels in Cerebrospinal Fluid of Patients With Alzheimer Disease (original) (raw)
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JAMA, 2003
HILE THE EXACT BIOLOGIcal cascade associated with Alzheimer disease (AD) is only partially understood, many potential biomarkers of this disease process are known. 1 Two of the most obvious candidates are -amyloid 1-42 and tau proteins, as they are intimately related to the pathognomonic features of amyloid plaques and neurofibrillary tangles in the AD brain. 2,3 Multiple previous studies have reported decreases in cerebrospinal fluid (CSF) measures of -amyloid. 4-7 Similarly, CSF measures of tau have routinely showed considerable elevations of this peptide in AD cases worldwide. 7-12 Some authors have reported that these 2 measures alone can accurately differentiate clinically diagnosed AD cases from controls more than 85% of the time. 7,13 Studies of CSF in AD patients have used widely varying methods and nomenclature for assessing and describ-Author Affiliations are listed at the end of this article.
Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia
Brain : a journal of neurology, 2015
Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set w...
Journal of Neurology, Neurosurgery & Psychiatry, 1998
Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Piteå River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease. Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year. Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism. CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia. The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease.
Annals of Neurology, 1998
To clarify the alterations of tau, amyloid β protein (Aβ) 1–40 and Aβ1–42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non‐AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme‐linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the Aβ1–42(43) levels and a significant increase of the ratio of Aβ1–40 to Aβ1–42(43) were observed in the AD patients. The longitudinal AD study showed continuous low Aβ1–42(43) levels and an increase of the ratio of Aβ1–40 to Aβ1–42(43) before the onset of AD. These findings suggest that CSF tau may increase wit...
Neurobiology of Aging, 2006
We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)--amyloid 1-42 (A 42 ), -total-tau (tau) and -phosphorylatedtau 181 (p-tau 181 ) as measured by sandwich ELISAs in the clinical routine of a community state hospital to discriminate between patients with Alzheimer's disease (AD), healthy controls (HC), non-AD-dementias, a group composed of various psychiatric disorders (non-AD-dementias, mental diseases) and an age-matched random sample (RS) (total N = 219).
Clinical Chemistry, 2001
Background: Tau protein and the 42-amino acid form of β-amyloid (Aβ42) measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical diagnostic markers for Alzheimer disease. For the introduction of these assays in clinical practice, adequate reference values are of importance. Methods: CSF samples were obtained from 231 neurologically and psychiatrically healthy individuals, 21–93 years of age, all with a MiniMental State examination score of 28 or above. Standardized ELISAs were used to measure tau and Aβ42 in CSF. Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10 fractiles were estimated to establish reference values for CSF-tau and CSF-Aβ42, respectively. Putative confounding factors, such as the influence of the passage of proteins from peripheral blood to CSF, influence of dysfunction of the blood-brain barrier, and freezing and thawing of CSF, were investigated. Results: A correlation with age was found for CSF-tau (r = 0.60; P...
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2011
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 dement...
P CSF Levels of Tau Protein and Beta Amyloid in Diagnosis of Alzheimer ́ S Disease
2004
About two thirds of cases of senile dementia are due to Alzheimer ́s disease (AD). Definite diagnosis of AD is based on the neuropathological changes in the brain characterized by the presence of senile amyloid plaques, neurofibrillary tangles and neuronal cell loss. Sensitive assays showed the presence of tau and beta amyloid in CSF and change in levels of these molecules have been suggested to be a possible markers of AD. Cerebrospinal fluid samples from total of 102 subjects consisting of 24 patients with AD and 78 control patients with other neurological diseases were examined by ELISA of tau protein and beta amyloid (Innogenetics, Belgium). As compared to the control group, the concentrations of tau protein were significantly higher in AD patients (p < 0.0001) in contrast to levels of beta amyloid, where are significantly decreased (p < 0.0001). ROC (Receiver Operating Characteristic) analysis was performed to define cut-off values for maximized sensitivity and specificit...
Blood amyloid and tau biomarkers as predictors of cerebrospinal fluid profiles
Journal of Neural Transmission, 2022
Introduction Blood biomarkers represent a major advance for improving the management, diagnosis, and monitoring of Alzheimer's disease (AD). However, their context of use in relation to routine cerebrospinal fluid (CSF) analysis for the quantification of amyloid peptides and tau proteins remains to be determined. Methods We studied in two independent cohorts, the performance of blood biomarkers in detecting “nonpathological” (A−/T−/N−), amyloid (A+) or neurodegenerative (T+ /N+) CSF profiles. Results Plasma Aβ1–42/Aβ1–40 ratio and phosphorylated tau (p-tau(181)) were independent and complementary predictors of the different CSF profile and in particular of the nonpathological (A−/T−/N−) profile with a sensitivity and specificity close to 85%. These performances and the corresponding biomarker thresholds were significantly different from those related to AD detection. Conclusion The use of blood biomarkers to identify patients who may benefit from secondary CSF testing represents...
Cerebrospinal fluid total tau as a marker of Alzheimer's disease intensity
International Journal of Geriatric Psychiatry, 2010
Objectives: The aim of this longitudinal study was to test the hypothesis that CSF biomarkers in AD patients also may be forward-looking measures that are associated not only with the degree and profile of cognitive impairment but also with changes in cognition over time.