共查询到20条相似文献,搜索用时 31 毫秒
1.
Jing L Luo J Zhang M Qin WJ Li YL Liu Q Wang YT Lawrence AJ Liang JH 《Neuroscience letters》2011,487(2):169-173
Cerebrospinal fluid (CSF) tau and phospho-tau levels have been associated with certain tau gene variants and low CSF amyloid-β (Aβ) levels in Alzheimer disease (AD), constituting potential biomarkers of molecular mechanisms underlying neurodegeneration. We aimed to assess whether such CSF-genetic endophenotypes are also present in Parkinson disease (PD). CSF tau, phospho-tau and Aβ levels were obtained from 38 PD patients (19 with dementia) using specific ELISA techniques. All cases were genotyped for a series of tau gene polymorphisms (rs1880753, rs1880756, rs1800547, rs1467967, rs242557, rs2471738 and rs7521). The A-allele rs242557 polymorphism was the only tau gene variant significantly associated with higher CSF tau and phospho-tau levels, under both dominant and dose-response model. This association depended on the presence of dementia, and was only observed in individuals with low (<500pg/mL) CSF Aβ levels. Such genetic-CSF endophenotypes are probably a reflection of the presence of AD-like molecular changes in part of PD patients in the setting of dementia. 相似文献
2.
Parnetti L Lanari A Silvestrelli G Saggese E Reboldi P 《Mechanisms of ageing and development》2006,127(2):129-132
Mild cognitive impairment (MCI) is an aetiologically heterogeneous syndrome. A correct prediction of MCI conversion to Alzheimer's disease (AD) represents a primary goal in routine clinical practice. Since the presence of pathological levels in >or=2 cerebrospinal fluid (CSF) biomarkers; amyloid protein (Abeta42), total tau (h-tau) and phospho-tau (p-tau) seems to reliably identifying MCI subjects converting to AD, we report our experience in a routine clinical setting. In the period from January 2001 to June 2003, 273 consecutive patients referred to our Memory Clinic for diagnostic assessment of cognitive impairment. Of them, 180 underwent a complete diagnostic evaluation including CSF dosage of fragment 1-42 of amyloid protein, total tau and phospho-tau (ELISA Method, Innogenetics, Gent, Belgium), after vascular or other secondary causes of dementia could be excluded. At baseline, 38% of the MCI subjects (20/55) showed pathological levels in >or=2 CSF biomarkers. After 1 year, 11 MCI patients converted to dementia, 33 remained stable, 11 showed a further progression of cognitive impairment still not fulfilling the diagnostic criteria for dementia. Of the 11 converters, 10 showed >or=2 pathological values CSF biomarkers and in all of them, p-tau was high. On the contrary, 29 out of 33 stable MCI (88%) showed no or one pathological CSF value. We confirm that pathological levels in >or=2 CSF biomarkers reliably predict MCI conversion to AD and correctly identify the stable form of MCI. 相似文献
3.
Are the CSF levels of 24S-hydroxycholesterol a sensitive biomarker for mild cognitive impairment? 总被引:1,自引:0,他引:1
Leoni V Shafaati M Salomon A Kivipelto M Björkhem I Wahlund LO 《Neuroscience letters》2006,397(1-2):83-87
There is a need for effective biomarkers showing whether or not a patient with mild cognitive impairment (MCI) will progress to Alzheimer's disease (AD) with dementia. At the present three cerebrospinal fluid (CSF) biomarkers are in general use: total tau, phospho-tau and beta-Amyloid. These markers are regarded to have high capacity to differentiate early AD from normal ageing. We have analysed CSF levels of a new marker for neuronal degeneration, 24S-hydroxycholesterol (24OHC) in patients with MCI. For reasons of comparison, we also analysed these levels in patients with AD. There was a significant correlation between CSF levels of 24OHC and total tau (as well as phospho-tau) in both groups of patients. Fifty percent of the patients contemplated for MCI were found to have elevated levels of 24OHC (using a 95th upper percentile set cut-off). All the MCI patients with normal levels of 24OHC had normal levels of the other markers. In patients with AD, the percentages of those with increased levels of 24OHC, tau and phospho tau were similar (55-67%). In this pilot study, we discuss the possibility that 24OHC may be a sensitive test for MCI. 相似文献
4.
Vilmantas Giedraitis Anna Glaser Timo Sarajärvi RoseMarie Brundin Malin Degerman Gunnarsson Brit-Maren Schjeide Rudolph E. Tanzi Seppo Helisalmi Tuula Pirttilä Lena Kilander Lars Lannfelt Hilkka Soininen Lars Bertram Martin Ingelsson Mikko Hiltunen 《Neuroscience letters》2010
Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimer's disease (AD). Moreover, the risk allele increased amyloid-β (Aβ) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate Aβ or tau levels in cerebrospinal fluid (CSF). Nearly 200 individuals with AD or other cognitive disorders were included for CSF analysis and CALHM1 genotyping. No significant differences in CSF levels of Aβ42, tau or phospho-tau were found across the various CALHM1 genotypes. In conclusion, we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated AD biomarkers. 相似文献
5.
It is generally accepted that cerebrospinal fluid (CSF) biomarkers such as tau protein, phosphorylated tau protein (threonine 181) and beta-amyloid (1-42) can facilitate early and differential diagnosis of Alzheimer's disease (AD). Since the respective concentrations can only be measured in a number of specialized centers, time to CSF specimen work-up has been considered as crucial for the stability of the respective biomarkers. When shipping of CSF samples is needed for biomarker measurement and immediate freezing of samples is not available, an overnight delay of up to 24h frequently occurs. Therefore, we investigated the potential impact of a 24h delayed freezing on CSF biomarker concentrations and compared it to 2h storage (room temperature, 20 degrees C) and an immediate freezing. First, storage at room temperature for 2h had only marginal, non-significant effects on the concentrations of CSF total tau protein and phospho-tau protein (181) compared to immediate freezing. Second, storage at room temperature for 24h did not significantly affect total tau protein or phospho-tau protein but beta-amyloid (1-42) concentrations which increased significantly compared to the samples frozen immediately. These results indicate that CSF samples for the evaluation of total tau and phospho-tau protein may be kept at room temperature for up to 24h whereas CSF samples for beta-amyloid (1-42) need to be frozen immediately. 相似文献
6.
Alzheimer's disease (AD) is characterized by neuronal loss and the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. Cerebrospinal fluid (CSF) levels of β-amyloid and tau/phospho-tau181 (ptau181) are also associated with AD. We have previously demonstrated that a single nucleotide polymorphism in calcineurin is associated with CSF ptau181 levels and AD progression. In this study, we demonstrate that calcineurin protein levels are inversely correlated with dementia severity and Braak tangle stage in AD brains, and calcineurin activity is globally reduced in AD brains. We then sought to model the observed changes in CSF tau by measuring extracellular tau in cultured cells. SH-SY5Y cells treated with calcineurin inhibitors produced reduced calcineurin activity and a corresponding increase in extracellular ptau181. These findings are consistent with our observations in AD patients, who have elevated CSF ptau181 and reduced calcineurin activity in brain extracts. Thus, we have identified a gene that contributes to AD pathology and has functional consequences on tau metabolism in cultured cells. 相似文献
7.
Blennow K Johansson A Zetterberg H 《International journal of molecular medicine》2005,16(6):1147-1149
Creutzfeldt-Jakob disease (CJD) is a fatal prion disease characterized by rapid neurodegeneration. The clinical diagnosis is difficult and reliable diagnostic markers are highly desired. Here, we assess the sensitivity, specificity and predictive values of cerebrospinal fluid (CSF) tests for 14-3-3 protein and total tau (T-tau)/phospho-tau (P-tau) ratio among 36 patients with clinically suspected CJD. Nine of the 36 patients had CJD. These cases were all autopsy-proven. The 14-3-3 test was positive in 4 of the 9 CJD cases and falsely positive in 7 of the 27 patients with other diagnoses. The resulting figures for sensitivity, specificity, and positive and negative predictive values were 44%, 74%, 36% and 80%, respectively. The best result for distinguishing CJD from other diagnoses was obtained using a combined test for T-tau and T-tau/P-tau ratio and cut-off values of >1,400 pg/ml and >25, respectively. The resulting figures for sensitivity, specificity, and positive and negative predictive values were 78%, 93%, 78% and 93%, respectively. The achieved accuracy (89%) was significantly higher than that for the 14-3-3 test (67%; P=0.023). The high predictive values achieved by the combined tau test suggest that it could be used in conjunction with other diagnostic methods for accurate intra vitam diagnosis of CJD. 相似文献
8.
Agitation and aggressive behavior are common symptoms of Alzheimer's disease (AD), and tangle density in frontal cortex is a possible regional substrate of these behaviors. To investigate this further, 16 AD patients, 8 patients with non-AD dementia, and 13 age-matched control subjects for frontal cortex and, respectively, 21, 7, and 6 patients for parietal cortex were analyzed for tau and phospho-tau by enzyme-linked immunosorbent assay (ELISA). Agitation/aggression was determined by the Present Behavioural Examination. In a subset of cases, glycogen synthase kinase-3β (GSK-3β) phosphorylation and protein phosphatase 2A (PP2A) expression were measured. Phospho-tau and the phospho-tau/total tau ratio were elevated in AD in both cortical regions. In keeping with our hypothesis, the phospho-tau/total tau ratio was elevated in the frontal cortex of those patients with agitation/aggression during life, and there was a significant correlation (p = 0.024) between these behaviors and the phospho-tau/total tau ratio in the cortex. PP2A expression was lower (p < 0.01) in the frontal cortex of patients with high tau phosphorylation. This study confirms a link between tau phosphorylation and agitation/aggression and suggests that reducing tau phosphorylation may provide symptomatic relief. 相似文献
9.
Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein, beta-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of both beta-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-beta-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases. 相似文献
10.
OBJECTIVE: Age-related changes of steroid levels in the central nervous system (CNS) are not well understood. To investigate whether steroidal conditions in the CNS of women change with aging and menopause, steroid levels have been measured in serum and cerebrospinal fluid (CSF), and examined correlations with aging. METHODS: Serum and CSF concentrations of estradiol (E2), cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS) and albumin were measured in 80 female patients who underwent operations for benign gynecological diseases. They had no endocrinological or neurological disorders and were aged 17-71 years; 62 patients were in premenopause and 18 were in postmenopause. RESULTS: Serum levels of E2 decreased markedly after menopause, while levels of DHEA and DHEAS decreased gradually with age. There was no significant change with age of serum cortisol levels. The CSF concentrations of E2 (0.2-3 pg/ml) decreased with age [correlation coefficient (r)= 0.31, P < 0.01]. The CSF DHEA levels (0.1-0.8 ng/ml) did not change with age although not significantly, but CSF cortisol levels (0.1-0.6 microg/dl) increased with age (r = 0.35, P < 0.01). The CSF DHEAS concentrations were below the sensitivity of the radioimmunoassay (RIA) (1 ng/ml). The CSF/serum ratios of cortisol increased with age (r = 0.30, P < 0.01), as did those of DHEA (r = 0.55, P < 0.01). Although serum albumin levels did not change throughout life, CSF albumin levels and CSF/serum albumin ratios increased gradually with age (r = 0.28, P = 0.052; r = 0.23, P = 0.114, respectively), but there was no significance. There were marked decreases of serum E2 and DHEA levels and CSF E2 levels in postmenopausal women (P < 0.05), but CSF cortisol levels increased (P < 0.05) and DHEA levels in CSF were maintained after menopause. CONCLUSION: These results indicate that steroids in CSF become cortisol dominated and deficient in estrogens with aging, especially after menopause. 相似文献
11.
Montine TJ Kaye JA Montine KS McFarland L Morrow JD Quinn JF 《Archives of pathology & laboratory medicine》2001,125(4):510-512
OBJECTIVE: To test the hypothesis that quantification of cerebrospinal fluid (CSF) F(2)-isoprostanes (F(2)-IsoPs), in vivo biomarkers of free radical damage, along with CSF Abeta(42) and tau levels improves laboratory diagnostic accuracy for Alzheimer disease (AD). PARTICIPANTS: Patients with probable AD (n = 19), dementias other than AD (n = 8), and age-matched controls (n = 10). MAIN OUTCOME MEASURES: Cerebrospinal fluid concentrations of Abeta(42) and tau were determined by a commercially available test (Athena Diagnostics, Worcester, Mass). Cerebrospinal fluid F(2)-IsoP levels were quantified by gas chromatography/mass spectrometry. RESULTS: Individuals were classified as AD or non-AD by a published method using CSF Abeta(42) and tau levels (95% sensitivity, 50% specificity), by CSF F(2)-IsoP levels greater than 25 pg/mL and Abeta(42) concentrations less than 1125 pg/mL (90% sensitivity, 83% specificity), and by combined analysis using CSF F(2)-IsoP, Abeta(42), and tau levels (84% sensitivity, 89% specificity). CONCLUSION: Cerebrospinal fluid F(2)-IsoP quantification may enhance the accuracy of the laboratory diagnosis of AD. 相似文献
12.
Roubaud-Baudron C Krolak-Salmon P Quadrio I Mégraud F Salles N 《Neurobiology of aging》2012,33(5):1009.e11-1009.e19
Recent case-control studies reported an association between H. pylori infection and Alzheimer's disease (AD). Our aim was to compare cognitive impairment, neuroinflammation, and cerebrovascular lesion load in a group of AD patients according to their H. pylori status. For the 53 AD patients included, we assessed: clinical data (vascular comorbidities and cognitive assessment), biological data (especially fibrinogen, homocysteine levels, apolipoprotein E4 genotype; cerebrospinal fluid [CSF] total tau protein [Tau], phospho-tau(181) protein [pTau(181)]), and amyloid beta peptide levels, serum/CSF-cytokines (interleukin [IL]-1β, IL-6, IL-8, tumor necrosis factor [TNF]-α) and pepsinogen I/pepsinogen II (PgI/PgII) ratio, and cerebrovascular lesion load (magnetic resonance imaging [MRI] fluid-attenuated inversion recovery [FLAIR] with the Fazekas and Schmidt scale). H. pylori infection was diagnosed by enzyme-linked immunosorbent assay (ELISA) and immunoblot test. H. pylori infection was associated with a decreased Mini Mental State Examination (MMS) (p = 0.024), and higher CSF pTau(181) (p = 0.014) and tau (p = 0.021) levels. A decreased PgI/II ratio (i.e., an increased gastric atrophy) was associated with the infection (p = 0.005). Homocysteine levels were positively correlated to Fazekas score (r = 0.34; p = 0.032) and to H. pylori immunoglobulin (Ig)G levels (r = 0.44; p = 0.001). Higher CSF cytokine levels (IL-8, p = 0.003; TNF-α, p = 0.019) were associated with the infection, but systemic inflammation results were controversial. Finally, in multivariate analysis, a lower MMSE score (odds ratio [OR], 0.83 [0.72-0.97]; p = 0.017), plasma IL-1β level (OR, 0.31 [0.11-0.87]; p = 0.025), an increased gastric atrophy, i.e., a lower PgI/PgII ratio (OR, 0.63 [0.43-0.93]; p = 0.020) were still associated with the infection. AD patients infected by H. pylori tended to be more cognitively impaired. Studies are needed to attest to the impact of H. pylori infection on AD course, especially on cerebrovascular lesions and neuroinflammation. 相似文献
13.
Schönknecht P Pantel J Hunt A Volkmann M Buerger K Hampel H Schröder J 《Neuroscience letters》2003,339(2):172-174
Cerebrospinal fluid tau protein levels are considered to be a promising marker for Alzheimer's disease (AD) and may facilitate early detection. Using the newly developed INNOTEST Phospho-Tau((181P)) kit examination of total tau and tau protein phosphorylated at threonine 181 (phospho-tau 181) revealed significantly (P<0.05) higher values in both patients with incipient and manifest AD than in controls. In patients with vascular dementia, phospho-tau 181 levels were not different from controls but were significantly lower than in patients with manifest AD. These findings suggest that total and phosphorylated tau protein may facilitate early detection and differential diagnosis of AD. 相似文献
14.
Ibach B Binder H Dragon M Poljansky S Haen E Schmitz E Koch H Putzhammer A Kluenemann H Wieland W Hajak G 《Neurobiology of aging》2006,27(9):1202-1211
We prospectively evaluated the diagnostic accuracy of cerebrospinal fluid (CSF)-beta-amyloid1-42 (Abeta42), -total-tau (tau) and -phosphorylated-tau181 (p-tau181) 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). By comparing patients with AD to HC as reference, tau revealed sensitivity (sens)/specificity (spec) of 88%/80%, p-tau(181) 88%/80%, tau/Abeta42-ratio 81%/85% and phospho-tau(181)/Abeta42-ratio 81%/78%. Discriminative power between HC and all dementias under investigation was estimated lower for tau (78%/77%) and p-tau(181) (73%/79%). Relative to patients with AD, ROC analysis for the RS revealed highest sens/spec for p-tau181 (79%/77%) and p-tau181/Abeta42 ratio (78%/75%). Differentiation between AD versus a group made of patients with various psychiatric disorders was optimised by using CSF-p-tau181 (80%/77%). Under clinical routine conditions current CSF-biomarkers show a substantial capacity to discriminate between AD and HC as reference and to mark off AD patients from RS and heterogeneous diagnostic groups composed of non-AD dementias and other psychiatric conditions. Despite a residual substantial overlap between the groups, we conclude that current CSF markers are well suited to support AD-related diagnostic procedures in every-day clinics. 相似文献
15.
Cleavage and conformational changes of tau protein follow phosphorylation during Alzheimer's disease 总被引:2,自引:0,他引:2
Mondragón-Rodríguez S Basurto-Islas G Santa-Maria I Mena R Binder LI Avila J Smith MA Perry G García-Sierra F 《International journal of experimental pathology》2008,89(2):81-90
Phosphorylation, cleavage and conformational changes in tau protein all play pivotal roles during Alzheimer's disease (AD). In an effort to determine the chronological sequence of these changes, in this study, using confocal microscopy, we compared phosphorylation at several sites (Ser(199/202/396/404/422)-Thr(205) and the second repeat domain), cleavage of tau (D(421)) and the canonical conformational Alz-50 epitope. While all of these posttranslational modifications are found in neurofibrillary tangles (NFTs) at all stages of the disease, we found significantly higher numbers of phospho-tau positive NFTs when compared with cleaved tau (P = 0.006 in Braak III; P = 0.002 in Braak IV; P = 0.012 in Braak V) or compared with the Alz-50 epitope (P < 0.05). Consistent with these findings, in a double transgenic mice model (Tet/GSK-3beta/VLW) overexpressing the enzyme glycogen synthase kinase-3beta (GSK-3beta) and tau with a triple FTDP-17 mutation (VLW) with AD-like neurodegeneration, phosphorylation at sites Ser(199/202)-Thr(205) was greater than truncated tau. Taken together, these data strongly support the notion that the conformational changes and truncation of tau occur after the phosphorylation of tau. We propose two probable pathways for the pathological processing of tau protein during AD, either phosphorylation and cleavage of tau followed by the Alz-50 conformational change or phosphorylation followed by the conformational change and cleavage as the last step. 相似文献
16.
Anomalously phosphorylated tau and Abeta fragments in the CSF correlates with cognitive impairment in MCI subjects 总被引:3,自引:0,他引:3
Maccioni RB Lavados M Guillón M Mujica C Bosch R Farías G Fuentes P 《Neurobiology of aging》2006,27(2):237-244
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of extracellular amyloid deposits, consisting largely of Abeta peptide and the presence of intraneuronal aggregates of neurofibillary tangles formed by tau. Development of cerebrospinal fluid (CSF) biomarkers has become a rapidly growing research field, considering the need for diagnostic tools for AD, thus allowing therapeutic compounds to have the greatest potential for being effective. We have focused on the relationships between critical biomarkers such as tau and Abeta in the CSF and the cognitive impairment of patients, as assessed by a battery of neuropsychological tests derived from CDR and CERAD, of value in the evaluation of AD patients. As part of a longitudinal study, we analyzed by ELISA and Western blots the levels and molecular patterns of hyperphosphorylated tau in the CSF of three different groups of patients: AD patients between 69- and 73-years-old, a group characterized with mild cognitive impairment (MCI) between 65- and 70-years-old, and a non-demented neurological control group of comparable ages. The levels of AT8-reactive phosphorylated tau were significantly higher (P<0.05) in AD patients (0.604+/-0.078, n=23) as compared with the control group (0.457+/-0.086, n=25). No differences between the levels of AT8-reactive tau of MCI patients (0.510+/-0.090, n=45) and controls were observed. However, when the MCI group was divided on the basis of the total box score (TBS) from CDR, those subjects with a TBS<1.5 presented tau levels (0.456+/-0.032, n=31) similar to controls, whereas those patients with TBS>or=1.5 displayed tau levels (0.590+/-0.086, n=14) comparable with those of AD. Western blot analyses revealed a higher AT8 reactivity in CSF samples of AD patients as compared with MCI and control samples, indicating higher levels of AD tau phosphoepitopes in the CSF. Tau heterogeneity was observed in samples of AD and MCI with higher impairment as compared with controls. As expected from previous reports, levels of Abeta (1-42) were lower (0.052+/-0.005) than controls (0.070+/-0.010), whereas the levels of MCI group were 0.060+/-0.007. The MCI group with a TBS>or=1.5 presented Abeta levels of 0.053+/-0.005 similar to those of AD patients, whereas the MCI group with TBS<1.5 exhibited Abeta levels (0.066+/-0.007) similar to controls. Studies highlight the relationships between anomalously phosphorylated tau markers in CSF with the information from TBS analysis of the different groups of patients. 相似文献
17.
de Souza LC Chupin M Lamari F Jardel C Leclercq D Colliot O Lehéricy S Dubois B Sarazin M 《Neurobiology of aging》2012,33(7):1253-1257
Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fluid (CSF) biomarkers are supportive features for the diagnosis of Alzheimer's disease (AD) and are assumed to be indirect pathological markers of the disease. In AD patients, antemortem MRI hippocampal volumes (HVs) correlate with the density of neurofibrillary tangles (but not with senile plaques) at autopsy suggesting that HVs may better correlate with CSF tau and hyperphosphorylated tau (P-tau) levels than CSF amyloid beta protein (Aβ)(42) level. Here, we tested this hypothesis in a well-defined AD group. Patients were selected according to the New Research Criteria for AD, including specific episodic memory deficit and CSF AD profile (defined as abnormal ratio of Aβ(42):tau). MRI was performed within 6 months of lumbar puncture. HVs were obtained using automated segmentation software. Thirty-six patients were included. Left HV correlated with CSF tau (R = -0.53) and P-tau (R = -0.56) levels. Mean HVs correlated with the CSF P-tau level (R = -0.52). No correlation was found between any brain measurement and CSF Aβ(42) level. The CSF tau and P-tau levels, but not the CSF Aβ(42) level, correlated with HV, suggesting that CSF tau markers reflect the neuronal loss associated with the physiopathological process of AD. 相似文献
18.
Relationship between apoE genotype and CSF beta-amyloid (1-42) and tau in patients with probable and definite Alzheimer's disease 总被引:4,自引:0,他引:4
Tapiola T Pirttilä T Mehta PD Alafuzofff I Lehtovirta M Soininen H 《Neurobiology of aging》2000,21(5):735-740
We investigated the usefulness of cerebrospinal fluid (CSF) beta-amyloid42 (Abeta42), beta-amyloid40 (Abeta40) and tau analyses in the diagnosis of Alzheimer's disease (AD). The study included 41 definite AD cases, 80 patients with probable AD. 27 with other dementias and 39 neurological controls. Abeta42, Abeta340 and tau protein concentrations in CSF were measured of using ELISA assays. Abeta42 levels were decreased and tau increased in AD. Combination of Abeta42 and tau resulted a sensitivity of 50.4% for AD and specificities of 94.8% for controls and 85.2% for other dementias. Ninety-one percent of the patients with Abeta42 below the cutoff value (340 pg/ml) and tau above the cutoff value (380 pg/ml) had AD. AD patients carrying apoE epsilon4 allele had lower Abeta42 (P < 0.005) and higher tau (P < 0.05) levels than those without an E4 allele, and 18 (81.8%) of the 22 AD patients who had normal Abeta42 and tau levels were apoE e4 allele non-carriers. Low Abeta42 and high tau concentration in CSF strongly support the diagnosis of AD. Measurement of Abeta42 may help the early diagnosis of cases at risk for AD such as apoE E4 allele carriers. 相似文献
19.
Shoji M Matsubara E Murakami T Manabe Y Abe K Kanai M Ikeda M Tomidokoro Y Shizuka M Watanabe M Amari M Ishiguro K Kawarabayashi T Harigaya Y Okamoto K Nishimura T Nakamura Y Takeda M Urakami K Adachi Y Nakashima K Arai H Sasaki H Kanemaru K Yamanouchi H Yoshida Y Ichise K Tanaka K Hamamoto M Yamamoto H Matsubayashi T Yoshida H Toji H Nakamura S Hirai S 《Neurobiology of aging》2002,23(3):363-370
A large scale multicenter study of cerebrospinal fluid (CSF) tau levels was conducted to determine the cut-off value, sensitivity and specificity for clinical usage as a biomarker of Alzheimer's disease (AD). Its use for early and differential diagnosis and the factors that increase CSF tau levels were also examined. CSF samples from a total of 1,031 subjects including 366 patients with AD, 168 patients with non-Alzheimer type dementia (NA), 316 patients with non-dementia neurological diseases (ND) and 181 normal controls (NC) were measured using ELISA for tau. The cut-off value of tau, 375 pg/ml, showed 59.1% sensitivity and 89.5% specificity for diagnosis of AD compared with the other groups. The tau levels were increased from the early to late stages of AD. Elevation of CSF tau in the non-tauopathy and tauopathy dementia groups, chronic and acute damage to the cerebrum, and meningeal disturbance were other factors that required attention for clinical practice. Measurement of CSF tau was useful as a biomarker for early and differential diagnosis of AD. 相似文献
20.
Christopher M. Acker Stefanie K. Forest Ray Zinkowski Peter Davies Cristina d'Abramo 《Neurobiology of aging》2013
Transgenic mouse models have been an invaluable resource in elucidating the complex roles of β-amyloid and tau in Alzheimer's disease. Although many laboratories rely on qualitative or semiquantitative techniques when investigating tau pathology, we have developed 4 Low-Tau, Sandwich enzyme-linked immunosorbent assays (ELISAs) that quantitatively assess different epitopes of tau relevant to Alzheimer's disease: total tau, pSer-202, pThr-231, and pSer-396/404. In this study, after comparing our assays with commercially available ELISAs, we demonstrate our assay's high specificity and quantitative capabilities using brain homogenates from tau transgenic mice, htau, JNPL3, and tau knockout. All 4 ELISAs show excellent specificity for mouse and human tau, with no reactivity to tau knockout animals. An age-dependent increase of serum tau in both tau transgenic models was also seen. Taken together, these assays are valuable methods to quantify tau and phospho-tau levels in transgenic animals, by examining tau levels in brain and measuring tau as a potential serum biomarker. 相似文献