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Biomedical subjects

E Patsouris

Publications and source records attributed to E Patsouris.

At least 37 records · Page 2Linked to original sources

Increased microvascular network in bone marrow of HIV-positive haemophilic patients.

OBJECTIVES: Angiogenesis has been associated with the pathogenesis of myelodysplastic syndromes (MDSs). However, less is known about the significance of this process in the bone marrow of HIV-positive patients with myelodysplastic features (MDF). METHODS: Trephines from 22 HIV-positive haemophilic patients were immunostained for CD34 antigen, and the microvessel density (MVD) was quantitatively evaluated and compared with that of 21 biopsies from patients with primary MDS and with that of 12 control bone marrows with no evidence of marrow disease. RESULTS: Bone marrow MVD in HIV-positive haemophilic patients was similar to that in patients with MDS; however, both groups revealed significantly higher MVD counts than those of control bone marrows (P=0.002). Mean MVD counts of HIV-positive haemophilic patients were significantly associated with HIV RNA levels (P=0.008). In contrast, no correlation was found between MVD and clinical HIV stage or CD4 counts at the time of biopsy. CONCLUSIONS: These results suggest a direct involvement of HIV in the pathogenesis of MDF in HIV infection. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients may provide further insights into the pathobiology of AIDS.

Adult↗

Clinicopathologic correlations of bone marrow angiogenesis in chronic myeloid leukemia: a morphometric study.

Various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemical staining, were evaluated in the bone marrow of 52 patients with chronic myeloid leukemia (CML) in chronic phase, in relation to several clinicopathologic parameters. Twenty control bone marrows and 15 cases of CML in blastic phase were also studied. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related parameters were quantitated in the region of most intense vascularization using image analysis. Overall, the group of chronic phase CML had higher MVD and size-related parameters and more branching microvessels than controls. Blastic phase was characterized by increased numbers of microvessels with a rounder shape and smaller caliber than chronic phase. A positive correlation emerged between marrow fibrosis and MVD as well as between white blood cell counts and rounder vessel sections. No relationship existed between microvascular parameters and Hasford or Sokal prognostic scores. In univariate analysis, overall and progression-free survival were adversely affected by MVD, size-related parameters, increased platelet count, age and spleen size. Multivariate analysis indicated that microvessel area was related to progression-free survival, whereas both MVD and area were significant prognosticators of overall survival, even when Hasford or Sokal scores are introduced into the model. Our data suggest that changes in angiogenic parameters may participate in the conversion of normal marrow to CML and ultimately to blastic transformation. More importantly, MVD and microvessel caliber are significant predictors of patient survival and progression.

Adolescent↗

Hormone receptors in non-malignant meningiomas correlate with apoptosis, cell proliferation and recurrence-free survival.

AIMS: A retrospective immunohistochemical and statistical analysis of patients with non-malignant meningiomas was undertaken to determine the correlation of steroid hormone receptor status with apoptosis, tumour cell proliferation, clinicopathological characteristics and prediction of recurrence. METHODS AND RESULTS: Paraffin sections from 51 primary intracranial totally resected benign and atypical meningiomas were immunohistochemically evaluated for the expression of progesterone (PR), oestrogen (ER) and androgen (AR) receptors, apoptotic rate, Bcl-2, p53 and Ki67 antigens. In addition to the above parameters, the mitotic index and the patients' clinicopathological data were statistically correlated and entered in a recurrence-free survival analysis. A high level of apoptotic cell death was associated with loss of PR expression by logistic regression analysis (P = 0.016). An inverse correlation existed between the mitotic index and PR counts (P = 0.009), while high Ki67 values correlated with increased ARs (P = 0.041). Atypical meningiomas had a lower ER staining score (P = 0.036). Multivariate analysis indicated that the absence of PR and large tumour size were significant factors for shorter disease-free intervals. CONCLUSIONS: The results suggest that ER expression is lost or reduced in atypical meningiomas, whereas loss of PR expression is an indicator of increased apoptosis and early recurrence. PRs and ARs may also influence tumour cell proliferation.

Apoptosis↗

Mitosin, a novel marker of cell proliferation and early recurrence in intracranial meningiomas.

The expression of mitosin, a novel proliferation-associated molecule was evaluated immunohistochemically in a consecutive series of 47 patients with primary intracranial benign and atypical meningiomas. Mitosin expression was correlated with proliferation markers Ki-67 (MIB-1), proliferating cell nuclear antigen (PCNA), topoisomerase IIalpha (TopoIIalpha) and mitotic index, as well as with standard clinicopathological parameters and patient outcome. Seven tumors recurred (14.8%) following gross total resection, within a follow-up period ranging from 21 to 108 months (median 60 months). The higher proliferation indices were obtained with mitosin and PCNA and the lower ones with TopoIIalpha. Mitosin labeling index (LI) ranged from 0.1 to 57% (median 3%), with a significant overlapping of values between grades. A significant positive correlation was shown between mitosin LI on the one hand and Ki-67 LI (p < 0.001), or the mitotic index (p = 0.027) on the other. The incidence of recurrence was higher in cases with a mitosin LI higher than 3% (p = 0.048). Univariate analysis disclosed mitosin LI (p = 0.033) along with the mitotic index (p = 0.024) and tumor size (p = 0.028) as significant predictors of shortened recurrence-free survival. In multivariate analysis, the labeling indices of mitosin (p = 0.035) and Ki-67 (p = 0.032), along with tumor size, were shown to provide independent prognostic information, beyond that obtained by standard clinical and pathological parameters. However, as indicated by factor analysis, the prognostic information yielded by mitosin was superior to that provided by the remaining proliferation markers (p = 0.041). We conclude that mitosin immunohistochemical expression, although failing to discriminate between benign and atypical meningiomas, may be of use as a novel cell proliferation marker and as a predictor of tumor recurrence.

Antigens, Neoplasm↗

Evaluation of the cyclin-dependent kinase inhibitor p21Cip1 in epithelial ovarian tumors of low malignant potential and adenocarcinomas.

OBJECTIVE: In view of the controversial information on the significance of the cyclin-dependent kinase inhibitor p21Cip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathological variables and prognosis of epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 82 primary ovarian adenocarcinomas were stained immunohistochemically for p21Cip1, p53 protein and Ki-67 antigen (a marker of cell proliferation). RESULTS: p21Cip1 levels were significantly higher in LMP tumors (p<0.001) as well as in early stage adenocarcinomas (p=0.021) and those associated with minimal residual disease (p=0.008). However, no relationship existed between p21Cip1 expression and the proliferation rate of adenocarcinomas or LMP tumors. In the vast majority of LMP tumors p21Cip1 expression was not accompanied by p53 accumulation. This p21Cip1-positive/p53-negative phenotype prevailed in the early stage (p=0.026), lower grade (p=0.018) adenocarcinomas as well as in those left with minimal residual disease (p=0.059). In patients with lower grade adenocarcinomas, decreased p21Cip1 expression was adversely related to poor overall survival on its own (p=0.0500) and when combined with p53 protein overexpression (p=0.0323). In multivariate analysis, only the stage remained as the independent predictor of survival. CONCLUSIONS: Decreased p21Cip1 expression is related to several indicators of aggressiveness in ovarian adenocarcinomas and seems to be differentially regulated in LMP tumors and adenocarcinomas. On the contrary, deregulation of p21Cip1 expression does not seem to participate in the pathogenesis of LMP tumors. Furthermore, although p21Cip1 alone or combined with p53 is of prognostic significance in lower grade adenocarcinomas, it does not appear to add to the information gained from traditional prognosticators.

Adenocarcinoma↗

p53 mutations detection in urinary bladder cancer in the Greek population: application of the NIRCA assay.

The aim of the present study was to assess the use of an alternative molecular approach for p53 mutation detection and to investigate the usefulness of p53 as a prognostic indicator in bladder cancer. We applied the NIRCA assay, which consists of two-step PCR amplification, transcription of the amplified sequence, hybridisation of the transcripts and treatment with RNAses which recognizes mismatches due to the presence of mutations. Results of molecular analysis are correlated with immunohistochemical findings, standard clinopathological parameters and survival. p53 mutations were detected in 42.4% of the 66 examined TCCs cases. We could not demonstrate any statistical relationship between the presence of p53 mutation and p53 protein overexpression, and tumor stage or grade. A trend towards higher mutation rate in higher grade tumours was observed, although this failed to reach statistical significance. Despite the observation that the alterations of p53 gene are associated features of aggressive phenotype of transitional cell carcinomas they do not seem to offer additional prognostic information.

Carcinoma, Transitional Cell↗

Apoptotic markers for tumor recurrence: a minireview.

The control of apoptotic mechanisms is integral to many aspects of tumor biology and appears to be involved in the process of recurrence. Apoptosis serves as an essential mechanism to prevent the proliferation of cells with a higher mutation rate, thus tempering malignant transformation. Most antineoplastic therapies function by triggering apoptosis in sensitive cells. Resistance to treatment may result from specific inhibition of apoptotic signaling. Chemotherapy or radiation may increase the mutation rate and hasten tumor evolution in cancer cells that are resistant to apoptosis. Summarizing the current evidence regarding the usefulness of various apoptotic markers for predicting tumor recurrence, the most extensively studied appear to be bcl-2 and p53, as well as the apoptotic rate itself, with promising prognostic potential in several neoplasias. Investigative results, however, mostly refer to multiple single-center retrospective studies, awaiting validation by large prospective clinical trials. Despite initial optimism, it becomes apparent that the measurement of one or more gene products is inadequate to directly predict a phenomenon as complex as the clinical outcome. One of the challenges that is only beginning to be addressed is the combined assessment of traditional prognostic parameters and molecular biomarkers by creating models or equations to predict the likelihood of recurrence. Such screening of patients may help define prognostic categories and influence treatment decisions.

Animals↗

Prognostic implications of microvessel morphometry in diffuse astrocytic neoplasms.

Astrocytic brain tumours, particularly malignant astrocytomas, are recognized to be highly vascular neoplasms with potent angiogenic activity. Recent research has shown that quantification of microvessel density (MVD), as a measure of the degree of angiogenesis, constitutes a strong prognostic indicator in patients with astrocytomas. However, the significance of other morphometric aspects of microvessel network has not been tested so far. In this report, histological sections from 70 astrocytomas (grades II to IV), immunostained for CD34, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to vessel size or shape. Minor axis length increased with grade (P = 0.045) but MVD and TVA presented a peak in grade III (P = 0.033 and P < 0.001, respectively). Size and shape related parameters affected survival in univariate analysis of grade IV and grades II/III, respectively. In multivariate analysis, only branching counts, along with age and grade, were the independent predictors of survival. Although MVD, TVA and branching counts were adversely related to disease-free survival in grades II and III (univariate analysis), only TVA remained statistically significant in multivariate analysis. It is concluded that TVA and branching counts are prognostically more informative than MVD for patients with diffuse astrocytic tumours.

Adolescent↗

Hypoxaemic reperfusion ameliorates the histopathological changes in the pig brain after a severe global cerebral ischaemic insult.

BACKGROUND AND PURPOSE: We have recently shown that hypoxaemic reperfusion, after an ischaemic brain insult, improves neurological outcome and decreases lipid peroxidation. In the present study, we investigated the effect of hypoxaemic reperfusion on brain histopathological changes. METHODS: Sixteen pigs subjected to a 10-min global cerebral ischaemia were either hypoxaemically (PaO2 = 35 mmHg, hypoxaemic reperfusion (HR) group, n = 8) or hyperoxaemically (PaO2 > 300 mmHg, control (C) group, n = 8) reperfused. The brains were removed 24 h after reperfusion and six neuropathological abnormalities were evaluated blindly and scored semi-quantitatively (0: normal to 3: severe injury) on eight representative regions of the brain. The overall cumulative score of the abnormalities and their regional prevalence, as well as the neurological outcome, were compared between the two groups. RESULTS: The neuronal degeneration, assessed in terms of cumulative score (P = 0.002) and regional prevalence (P = 0.025 to P = 0.041), was lower in the HR group than in the C group. Spongy degeneration attained statistically significant difference only in cerebellum (P = 0.002) and inflammation only in hippocampus (P = 0.046) but the difference in the cumulative score of these abnormalities was not statistically significant. The difference of the three neurological assessments over time was statistically significant between the two groups, i.e. after resuscitation (P = 0.001), at 8 h (P = 0.006) and at 24 h (P = 0.001) after reperfusion. CONCLUSIONS: Hypoxaemic reperfusion during resuscitation from a severe global ischaemic cerebral insult is associated with statistically significantly fewer histopathological changes of the brain than in controls. This is associated with a superior neurological outcome.

Animals↗

Morphometric microvascular characteristics predict prognosis in superficial and invasive bladder cancer.

Recent research has shown that neovascularization, quantitated by microvessel density (MVD), constitutes a strong prognostic indicator in patients with invasive urothelial carcinomas. These studies, however, have focused only on MVD as the only factor reflecting angiogenesis in transitional-cell carcinomas (TCCs). The objective of this report was to evaluate multiple morphometric microvascular characteristics besides MVD in superficial and muscle-invasive TCCs separately, to provide a better approach to the relationship between angiogenesis, clinicopathological parameters, and prognosis. Histologic sections from 115 TCCs [35 superficial (T1) and 80 muscle-invasive] were immunostained for CD31 and evaluated using image analysis for the quantitation of MVD, area, total vascular area, major axis length, minor axis length, perimeter, compactness, shape factor, and Feret diameter. Patients were followed-up until death (n=31) or for an average of 42.2 months (median 38.5 months). MVD increased with progressing T category (P=0.049) but area (P=0.033), major axis length (P=0.022), perimeter (P=0.043), and Feret diameter (P=0.042) were highest in T2 tumors. Area was the single independent predictor of adverse significance in T1 TCCs, whereas for muscle-invasive tumors, survival was independently predicted by MVD. Regarding disease-free survival in superficial tumors, the single significant independent parameter was compactness, whereas area was an independent favorable indicator of disease-free survival for patients with invasive TCCs. It is concluded that the prognostic significance of neovascularization is better assessed by area and shape-related morphometric characteristics, whereas MVD becomes influential only with regard to overall survival of patients with invasive tumors.

Adult↗

Apoptosis detected with monoclonal antibody to single-stranded DNA is a predictor of recurrence in intracranial meningiomas.

Precise quantitation of apoptotic cells in meningiomas is necessary to determine the role of apoptosis in tumor growth and recurrence. In this study, we investigated the incidence of baseline apoptosis in relation to p53 and bcl-2 protein expression, proliferation status as expressed by Ki-67, PCNA and mitotic counts, standard clinicopathological parameters and patients' outcome, in a series of 59 patients with primary intracranial benign and atypical meningiomas. Seven tumors recurred (11.9%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months. Apoptotic fractions were quantified immunohistochemically by means of a novel monoclonal antibody recognizing exposed single-stranded (ss) regions in the DNA of apoptotic cells during heating. Tissues consisted of archival formalin-fixed paraffin-embedded meningioma specimens. The apoptotic index (AI) ranged from 0% to 2.90% (mean: 0.50%), increased with proliferative activity (p = 0.014), had lower values in transitional meningiomas (p = 0.001) and was unrelated to grade and p53 expression. Increased AI predominated among bcl-2 negative tumors (p = 0.041) and tended to be accompanied by a shortened recurrence-free survival, in univariate (p = 0.0407) as well as in multivariate analysis (p = 0.0405). These results implicate apoptotic rate in meningioma growth and recurrence and denote that assessment of apoptotic potential by means of anti-ssDNA monoclonal antibody provides valid prognostic information irrespective of other parameters.

Adult↗

Prognostic evaluation of the microvascular network in myelodysplastic syndromes.

Considering the recently stated suggestion of neovascularization being implicated in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple morphometric microvascular characteristics in MDS, in relation to clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS patients were immunostained for factor VIII and compared to those from 20 controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia (AML) patients. Quantitation of microvessel density (MVD), area, total vascular area (TVA), major and minor axis length, perimeter, compactness, shape factor, Feret diameter, and the number of branching vessels was performed by image analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis and shape factor values and significantly lower compactness than the control group. AML was characterized by increased vascularity compared to MDS and CMML, as well as by the presence of flattened microvessels (lower values of shape factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber vessels than RAEB, which explains the favorable prognostic effect of increased size-related parameters on progression and/or survival. Moreover, decreased compactness and MVD were independent predictors of longer progression-free survival. It is concluded that angiogenesis is involved in the conversion of normal marrow to MDS and ultimately to AML and that disease progression within MDS is accompanied by qualitative alterations of the microvascular network. Furthermore, size-related parameters affect survival, while shape-related parameters and MVD are more influential with regard to progression-free survival.

Acute Disease↗

Myelodysplastic features in patients with long-term HIV infection and haemophilia.

HIV-related bone marrow changes are consistent with myelodysplastic features (MDF). Their pathogenesis may differ from primary myelodysplastic syndromes (MDS) and is associated with various factors including the virus itself or the antiretroviral therapy. In order to evaluate the differences between HIV-related MDF and MDS, the morphological changes in peripheral blood and bone marrow, cytogenetic analysis and the response to anaemia treatment were studied in 158 HIV+ patients with haemophilia and the results were compared with those of 61 patients with primary MDS (31 with RA, 10 with RARS, 11 with RAEB, three with RAEB-t and six with CMML). The eligibility criteria for patients with MDS were primary MDS, Hb levels < 10 g dL(-1), and no significant organ disease. The peripheral blood and bone marrow examination revealed MDF in 44 HIV-infected haemophilic patients (27.8%). The median time from seroconversion was 12.5 years and the mean time under AZT therapy was 44.1 months. Nineteen of these patients (43.1%) had Hb levels < 10 g dL(-1), while neutropenia and thrombocytopenia were observed in 29.5% and 25%, respectively. Every patient of this study with Hb < 10 g dL(-1) received erythropoietin (Epo). There were statistically significant morphological alterations between HIV-related MDF and MDS: hypocellularity, plasmatocytosis and eosinophilia were more pronounced in HIV haemophiliacs with MDF, while dysplasia of erythroblasts, megakaryocytes and granulocytes was more frequent in MDS patients. No HIV haemophilic patient with MDF had more than 5% blasts in the bone marrow nor did any develop RAEB or acute leukaemia during the period of this study. The cytogenetic analysis was normal in HIV-infected patients with haemophilia whereas 42.6% of patients with MDS had an abnormal karyotype. Complete erythroid response was achieved with Epo administration in 84.2% of HIV+ haemophilic patients with anaemia compared to 19.7% of patients with MDS. These data suggest that bone marrow changes in long-term HIV patients have different characteristics from primary MDS and constitute the entity for which the name HIV-myelopathy has been proposed in the literature.

Aged↗

Evaluation of DNA topoisomerase IIalpha expression provides independent prognostic information in non-Hodgkin's lymphomas.

AIMS: In view of the dual role that DNA topoisomerase IIa (TopoIIa) plays as a cell proliferation marker and as a possible indicator of chemosensitivity, we investigated its expression in non-Hodgkin's lymphomas (NHL) in relation to conventional clinicopathological parameters, cell proliferation (as defined by Ki67 immunoreactivity), response to therapy and patient outcome. METHODS AND RESULTS: Formalin-fixed paraffin-embedded tissues from 153 patients with NHL were immunohistochemically stained for TopoIIalpha. Patients were followed up until death (n = 63) or for an average of 68 months (median 64 months, n = 90). The percentage of TopoIIalpha positive cells (TopoIIalpha LI) increased with grade (P < 0.001), extranodal location (P = 0.05) and Ki67 LI (P = 0.01, r = 0.673). In most cases (58%), Ki67 LI exceeded TopoIIalpha LI (TopoIIalpha/Ki67 < 1), especially within the indolent group (P < 0.001). TopoIIalphaLI, Ki67LI and TopoIIalpha/Ki67 ratio were all adversely related to overall survival in univariate analysis, though their significance was not maintained after adjustment for grade. In multivariate analysis high TopoIIalpha/Ki67 ratio and high TopoIIalpha LI independently predicted shortened overall and post-relapse survival, respectively. Most importantly, low TopoIIalpha/Ki67 ratio was the only independent predictor of diminished disease-free survival. However, there was no relationship between TopoIIalpha expression and response. CONCLUSIONS: Our results suggest that evaluation of TopoIIalpha expression and TopoIIalpha/Ki67 ratio as cell proliferation markers provides independent prognostic information in relation to post-relapse and overall survival. Furthermore, TopoIIalpha/Ki67 ratio appears to play a key role in the identification of patients prone to early relapse.

Adolescent↗

DNA topoisomerase IIalpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas.

AIMS: To assess the value of topoisomerase IIalpha (TopoIIalpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 (MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore, to investigate its relation to standard clinicopathological parameters and patients' outcome. METHODS AND RESULTS: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoIIalpha and the higher ones with PCNA. TopoIIalpha labelling index (LI) ranged from 0.1% to 10% (median 0.5%) and, along with Ki67 and PCNA LI, increased with malignancy grade (P=0.049, P=0.045 and P < 0.001, respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoIIalpha and Ki67 (P < 0.001) or PCNA (P=0.032). In univariate and multivariate survival analysis, TopoIIalpha failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. CONCLUSIONS: TopoIIalpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However, it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67.

Antigens, Neoplasm↗

Mitosin and DNA topoisomerase IIalpha: two novel proliferation markers in the prognostication of diffuse astrocytoma patient survival.

The expression of two novel proliferation-associated markers, mitosin and topoisomerase IIalpha (Topo IIalpha), was evaluated immunohistochemically in consecutive paraffin sections from 60 diffuse astrocytomas (grades 2 to 4) in relation to clinicopathologic parameters, proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1) expression and survival. The percentage of mitosin and Topo IIalpha-positive cells (LI) increased with grade and Ki-67 LI, but could not discriminate between grade 3 on the one hand and grades 2 or 4 on the other hand. In 51% of cases, Ki-67 LI exceeded Topo IIalpha LI, especially within grade 4. Topo IIalpha and mitosin expression was adversely related to overall and disease-free survival in the entire cohort and in grades 2/3. However, only Topo IIalpha LI affected disease-free survival in grade 4 tumors. Multivariate analysis selected only mitosin LI along with the age of the patient, as the independent parameters predicting overall survival, whereas Topo IIalpha emerged as the single independent predictor of disease-free survival. It is concluded that the proliferative potential of astrocytomas, as measured by mitosin and Topo IIalpha immunostaining, conveys useful prognostic information, in addition to that obtained by standard clinicopathologic parameters.

Antigens, Neoplasm↗

Highly increased CSF tau protein and decreased beta-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease?

The aim was to quantify tau protein and beta-amyloid (Abeta42) in the CSF of patients with sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), and controls. Double sandwich enzyme linked immunosorbent assays (ELISAs) were used for measurements. Tau was increased 58-fold in CJD and 3.5-fold in AD compared with controls, whereas Abeta42 was decreased 0.5-fold in both CJD and AD. A cut off level for tau protein at 2131 pg/ml successfully discriminated CJD from AD (100% specificity and 93% sensitivity). Tau protein concentration in CSF is probably an additional useful marker in differentiating CJD from AD.

Aged↗