Normal Control Cases Research Articles

PAW37 Microarray analysis identifies the gene signature of spared vs vulnerable motor neurone groups

Motor neurone disease (MND) is characterised by the progressive degeneration of upper and lower motor neurones in the motor cortex, brain stem and spinal cord. However motor neurone groups such...

Cloning and expression of human filaggrin gene and detection of anti-filaggrin antibodies for diagnosis of rheumatoid arthritis

Objective To construct the recombinant plasmid containing human filaggrin gene,purify and identify the immunoreactivity of the recombinant protein,and establish the indirect ELISA to detect AFA for diagnosis of RA.Methods The constructed plasmids were transformed into E. Coli Rosettagami(DE3).This fusion protein was purified by NAT chromatography.ELISA coated with the fusion protein Was established to detect the AFA in serum of patients,which included 114 cases of RA,56 cases of SLE,32 cases of OA and 40 cases of normal controls. The correlation between the results of AFA and anti-CCP in RA group were compared. Results 321 bp fragment of filaggrin gene was amplified and the recombinant expression vector pET-28a( + )-filaggrin was constructed. The sequence of filaggrin gene was the same as the sequence reported in the literatures. The Rosetta-gami (DE3) strains of E. Coli with recombinant vector showed high level of filaggrin protein after induction. The SDS-PAGE showed that the plasmid expressed the filaggrin fusion protein with molecule weight of 14 000 Da. The expression protein could be purified by Ni-NAT with activity. The absorbance value of AFA in RA group was 0.473 ±0. 248 while they were 0. 160 0. 088, 0. 121±0. 070, 0.050 0. ±018 in SLE, OA and normal groups respectively. There were significant differences of absorbance values of AFA between RA and SLE, OA, control group (t = 12.004, 14. 464, 18.078, P<0. 01, respectively). The positivities of anti-filaggrin in RA, SLE and OA were 48.2%, 5.4% and 3. 1% respectively. The positivities of AFA were significantly different between RA, OA and normal control groups (x~2 = 67. 088, P < 0. 01). There was positive correlation of results between AFA and anti-CCP antibody (r = 0.42, P < 0. 05 ) . The consistency rate of results between AFA and anti-CCP was 70. 1%. Anti-CCP was negative in 10 out of 114 patients with AFA positive. AFA can be used to diagnose RA with sensitivity of 48. 2% , specificity of 96.9% , positive predictive value of 93. 2% and negative predictive values of 67. 9% . Conclusions The purified human filaggrin fusion protein is successfully purified. The indirect ELISA method based on the recombinant protein shows good sensitivity and specificity. Joint detection with AFA and anti-CCP can improve the positive rate of detection. Key words: Arthritis, rheumatoid; Intermediate filament proteins; Enzyme-linked immunosorbent assay

Computer-aided detection of architectural distortion in prior mammograms of interval cancer.

Architectural distortion is an important sign of breast cancer, but because of its subtlety, it is a common cause of false-negative findings on screening mammograms. This paper presents methods for the detection of architectural distortion in mammograms of interval cancer cases taken prior to the detection of breast cancer using Gabor filters, phase portrait analysis, fractal analysis, and texture analysis. The methods were used to detect initial candidates for sites of architectural distortion in prior mammograms of interval cancer and also normal control cases. A total of 4,224 regions of interest (ROIs) were automatically obtained from 106 prior mammograms of 56 interval cancer cases, including 301 ROIs related to architectural distortion, and from 52 prior mammograms of 13 normal cases. For each ROI, the fractal dimension and Haralick's texture features were computed. Feature selection was performed separately using stepwise logistic regression and stepwise regression. The best results achieved, in terms of the area under the receiver operating characteristics curve, with the features selected by stepwise logistic regression are 0.76 with the Bayesian classifier, 0.73 with Fisher linear discriminant analysis, 0.77 with an artificial neural network based on radial basis functions, and 0.77 with a support vector machine. Analysis of the performance of the methods with free-response receiver operating characteristics indicated a sensitivity of 0.80 at 7.6 false positives per image. The methods have good potential in detecting architectural distortion in mammograms of interval cancer cases.

Does Defective Apoptosis Play A Role in Cystic Fibrosis Lung Disease?

Although apoptotic dysfunction has recently been suggested in cystic fibrosis (CF), there are few studies reported concerning apoptosis in CF with controversial results. The aim of this study was to investigate apoptosis in CF human lung tissues and compare with non-CF bronchiectatic and normal healthy lung tissues. We also investigated the relation between apoptosis and histopathological features of tissues and microbiological factors influencing apoptosis. Lung tissue samples from CF (n=30), non-CF bronchiectasis (n=28, BE group) and normal control cases (n=24, C group) were included in the study. Histological examination of H & E-stained archived slides was performed and TUNEL method was used to detect DNA fragmentation. Apoptotic alveolar epithelial cells were significantly increased in the CF group compared to BE and C groups (p=0.046). Bronchopneumonia (BP) was present in 15 CF cases (50%), whereas none of the cases in C group had BP (p=0.0001). Apoptosis was significantly increased in cases with BP (n=17) compared to cases without BP (n=65) (p=0.04). Apoptotic epithelial cells and BP were significantly increased in the CF group and excess level of apoptosis may be the result of enhanced occurrence of BP. Apoptotic cells were alveolar epithelial cells in the great majority of the patients and were not detected in other locations where CFTR expression is much more prominent than alveolar cells. We may postulate that increased apoptotic findings in the alveolar epithelium were related with the presence of chronic infections rather than CFTR dysfunction.

Chromosome 17 Aberration of Oral Squamous Cell Carcinoma in Malaysia

In most tumours including Oral squamous cell carcinoma (SCC), acquisition of genetic instability is an essential step during carcinogenesis that involves generalized increased rate of errors during DNA replication, and defective repair of DNA. The genomic change results in numerical and structural chromosomal alterations, particularly in chromosomes 3, 9, 11 and 17. Chromosome 17 abnormality was chosen in my study because it shown strong correlation with neoplastic development and progression. In my study, twenty Oral SCC archival blocks were selected retrospectively from two referred Malaysian oral cancer centres. Histopathological findings were prior diagnosed by experienced Oral Pathologist, then Fluorescent in-situ Hybridization (FISH) technique was conducted subsequently by using specific probe of chromosome 17 in these oral SCC cases. In this study, the numerical aberration of chromosome 17 by FISH method in oral SCC in apparently normal tissues was evaluated. In this study, normal control cases showed 67.8±11% cells of disomic signals in their nuclei, whereas the numerical aberration of chromosome 17 is frequent demonstrated in oral SCC (17/20, 85%) cases. In hence, FISH can be used as a possible prognostic marker for the degree of genomic instability and aneuploidy in excised specimens of oral SCC containing invasive cancer in Malaysia.

Urine carcinoembryonic antigen determination in urinary bladder bilharziasis predicts carcinoma in patients with premalignant lesions: Observation of 43 cases in Egypt

Both urinary bilharziasis and urothelial neoplasia are associated with increased production of tissue carcinoembryonic antigen (CEA). Urine and serum CEA were determined in 43 patients with urinary bladder carcinoma including 22 post bilharzial and 21 non-biharzial cases, in addition to 10 normal control cases. A significant increase was detected in both urine and serum CEA levels with bladder carcinoma compared to control cases. Urinary CEA was significantly elevated in 86% of bilharzial versus 62% in nonbilharzial bladder carcinoma. Only 10.5% of control cases had urinary CEA elevation. The mean urinary CEA in bilharzial was higher than that of nonbilharzial carcinoma, but the difference was not statistically significant. There was a definite relationship between urine CEA and the stage of malignancy; the higher the stage, the higher the level of urine CEA. No relationship could be detected between the stage of malignancy and serum CEA, or between the grades of malignancy and urine or serum CEA levels. In conclusion, urinary CEA is more useful than serum CEA in the early detection of bilharziasis-associated urothelial carcinoma.

Relationship between SNP rs10774671 on OAS-1 gene and spontaneous HBeAg seroconversion in chronic HBV infection

To investigate the relationship between the SNP rs10774671 on OAS-1 gene and spontaneous HBeAg seroconversion in chronic HBV infection. Blood samples were collected from 58 HBeAg positive, 68 anti-HBe positive patients with chronic HBV infection, and 72 normal control cases without HBV infection. Chromosomal DNA was extracted and OAS-1 gene was amplified. SNP genotyping was performed with the competitively differentiated polymerase chain reaction and enzyme immunoassay. In HBeAg positive group, frequencies of genotype GG plus GA and allele G were 31.0% and 16.4%. They were 48.5% and 29.4% in anti-HBe positive group, and 50.0% and 28.4% in normal control group respectively. Differences between HBeAg positive group and anti-HBe positive group or normal control group were statistically significant. But they weren't between anti-HBe positive group and normal control group. Allele G on SNP rs10774671 of OAS-1 gene maybe benefits patients with chronic HBV infection to achieve spontaneous HBeAg seroconversion. Genotyping on this SNP may be predicting valuable for interferon therapy for chronic HBV infection.

The collection and processing of human brain tissue for research

To further understand the neuroanatomy, neurochemistry and neuropathology of the normal and diseased human brain, it is essential to have access to human brain tissue where the biological and chemical nature of the tissue is optimally preserved. We have established a human brain bank where brain tissue is optimally processed and stored in order to provide a resource to facilitate neuroscience research of the human brain in health and disease. A donor programme has been established in consultation with the community to provide for the post-mortem donation of brain tissue to the brain bank. We are using this resource of human brain tissue to further investigate the basis of normal neuronal functioning in the human brain as well as the mechanisms of neuronal dysfunction and degeneration in neurodegenerative diseases. We have established a protocol for the preservation of post-mortem adult human brain tissue firstly by snap-freezing unfixed brain tissue and secondly by chemical fixation and then storage of this tissue at -80 degrees C in a human brain bank. Several research techniques such as receptor autoradiography, DNA and RNA analysis, are carried out on the unfixed tissue and immunohistochemical and histological analysis is carried out on the fixed human tissue. Comparison of tissue from normal control cases and from cases with neurodegenerative disorders is carried out in order to document the changes that occur in the brain in these disorders and to further investigate the underlying pathogenesis of these devastating neurological diseases.

Dorsomedial SCN neuronal subpopulations subserve different functions in human dementia

The suprachiasmatic nuclei (SCN) are necessary and sufficient for the maintenance of circadian rhythms in primate and other mammalian species. The human dorsomedial SCN contains populations of non-species-specific vasopressin and species-specific neurotensin neurons. We made time-series recordings of core body temperature and locomotor activity in 19 elderly, male, end-stage dementia patients and 8 normal elderly controls. Following the death of the dementia patients, neuropathological diagnostic information and tissue samples from the hypothalamus were obtained. Hypothalamic tissue was also obtained from eight normal control cases that had not had activity or core temperature recordings previously. Core temperature was analysed for parametric, circadian features, and activity was analysed for non-parametric and parametric circadian features. These indices were then correlated with the degree of degeneration seen in the SCN (glia/neuron ratio) and neuronal counts from the dorsomedial SCN (vasopressin, neurotensin). Specific loss of SCN neurotensin neurons was associated with loss of activity and temperature amplitude without increase in activity fragmentation. Loss of SCN vasopressin neurons was associated with increased activity fragmentation but not loss of amplitude. Evidence for a circadian rhythm of vasopressinergic activity was seen in the dementia cases but no evidence was seen for a circadian rhythm in neurotensinergic activity. These results provide evidence that the SCN is necessary for the maintenance of the circadian rhythm in humans, information on the role of neuronal subpopulations in subserving this function and the utility of dementia in elaborating brain-behaviour relationships in the human.

VEGF Expression Correlates With Microvessel Density in Philadelphia Chromosome–Negative Chronic Myeloproliferative Disorders

We examined microvessel density (MVD) and immunohistochemical expression of vascular endothelial growth factor (VEGF) in the bone marrow biopsy specimens of 98 patients with Philadelphia chromosome-negative (Ph-) chronic myeloproliferative disorders (CMPDs). There were significantly more MVD "hot spots" in chronic idiopathic myelofibrosis (CIMF; mean +/- SD, 25.6 +/- 6.3) and polycythemia vera (PV; 20.7 +/- 10.2) cases than in essential thrombocythemia (ET) cases (10.1 +/- 4.5) and normal control (NC) samples (7.5 +/- 3.6) (P < .05). Similar results were found using a semiquantitative method (P < .0001). A calculated VEGF index (VEGF(i)) was higher in CIMF (0.29 +/- 0.15) and PV (0.28 +/- 0.20) cases than in ET (0.12 +/- 0.05) and NC (0.08 +/- 0.04) cases (P < .0001). MVD and VEGF(i) were higher in the myelofibrotic phases of CIMF and PV. There was a direct correlation between VEGF(i) and MVD when considering the Ph- CMPDs together (r = 0.67; P < .001) and when considering PV (r = 0.79; P < .001) and CIMF (r = 0.40; P = .013) as individual entities. Our data could provide a rationale for directly targeting VEGF or endothelial cells in CIMF and PV.

Postmortem Delay Has Minimal Effect on Brain RNA Integrity

The Bryan Alzheimer Disease Research Center obtains postmortem human brain tissue from patients with Alzheimer disease (AD) and cognitively normal control subjects for molecular and genetic research programs. A growing body of research suggests that variations in gene transcript levels may contribute to the onset and progression of disease. Identifying how the regulation of gene expression may affect AD requires the use of high-quality mRNA from banked human brains. The present study was conducted to establish the quality and suitability of available banked brain tissue for future gene expression studies. We chose 32 AD cases with Braak stage IV, V, or VI. These AD cases were matched to 36 normal control cases by age and sex when possible. Multiple regions from each brain were sampled, including frontal cortex, temporal cortex, occipital cortex, and cerebellum. Hippocampus was also available for study from 14 control cases. A comparison of several antemortem and postmortem variables, such as postmortem interval, agonal state, ventricular cerebrospinal fluid pH, and cause of death were analyzed. RNA was isolated from at least 1 area from every brain and most brains yielded intact RNA from all regions tested. Analysis of the clinical variables did not reveal any features that correlated with the ability to recover intact mRNA. We conclude that undegraded mRNA may be isolated from most brain regions many hours postmortem and that neither the pH of ventricular fluid nor postmortem interval is predictive of mRNA integrity.

TDP-43 immunoreactivity in neurodegenerative disorders: disease versus mechanism specificity

TDP-43 immunoreactivity in neurodegenerative disorders: disease versus mechanism specificity

Identification of the high-risk group for metastasis of gastric cancer cases by vascular endothelial growth factor receptor-1 overexpression in peripheral blood

Identification of an isolated tumour cell with metastatic ability is important for predicting the recurrence and prognosis of gastric cancer. A biological marker for evaluating the metastatic ability of gastric cancer cells has not yet been identified. We assessed vascular endothelial growth factor receptor-1 mRNA expression by quantitative real-time reverse transcriptase-polymerase chain reaction. Vascular endothelial growth factor receptor-1 mRNA in peripheral blood was more highly expressed in perioperative metastasis-positive and postoperative recurrence cases than in normal control cases, early cancer cases and nonmetastatic advanced cancer cases. The peripheral blood vascular endothelial growth factor receptor-1 mRNA-positive group was associated with advanced clinical stage, deep invasion beyond the muscularis propria, lymphatic involvement, vascular involvement, lymph node metastasis, positive peritoneal lavage cytology, preoperative metastasis and postoperative recurrence. Flow cytometry analysis disclosed that vascular endothelial growth factor receptor-1 expressing cells in the peripheral blood were more abundant in cancer cases with metastases than in cases without metastases. Our data suggest that the amount of positive cells may provide information on the clinical features of gastric cancer, especially in regard to gastric cancer metastasis.

Urine carcinoembryonic antigen levels are more useful than serum levels for early detection of Bilharzial and non-Bilharzial urinary bladder carcinoma: Observations of 43 Egyptian cases

BackgroundBoth urinary bilharziasis and urothelial neoplasia are associated with increased production of tissue carcinoembryonic antigen (CEA).Patients and methodsUrine and serum CEA were determined in 43 patients with urinary bladder carcinoma including 22 post bilharzial and 21 nonbiharzial cases, in addition to 10 normal control cases.ResultsA significant increase was detected in both urine and serum CEA levels with bladder carcinoma compared to control cases. Urinary CEA was significantly elevated in 86% of bilharzial, versus 62% in nonbilharzial bladder carcinoma. Only 10.5% of control cases had urinary CEA elevation. The mean urinary CEA in bilharzial, was higher than that of nonbilharzial carcinoma, but the difference was not statistically significant. There was a definite relationship between urine CEA and the stage of malignancy; the higher the stage, the higher the level of urine CEA. No relationship could be detected between the stage of malignancy and serum CEA, or between the grades of malignancy and urine or serum CEA levels.ConclusionUrinary CEA is more useful than serum CEA in the early detection of urotherlial carcinoma particularly if provoked by bilharziasis. Its level is also correlated with the tumor stage.

Volumetric analysis of septal region in schizophrenia and affective disorder

MRI and post-mortem studies indicate an increased prevalence of cavum septi pellucidi (CSP) in schizophrenia and affective disorder. The aim of this study was to characterize the CSP and the septal tissue among patients with schizophrenia, patients with affective disorder, and control subjects. The volumes of CSP and septal tissue were measured in post-mortem brains in 42 patients with schizophrenia, 14 patients with affective disorder, and 17 normal control cases by planimetry of serial sections. Enlargements of CSP (>100 mm(3)) were found in eight of the 42 (19%) patients with schizophrenia. There were no significant differences in CSP volumes between patients with affective disorder and controls. Enlarged CSP in schizophrenia were not associated with reduced septal tissue volumes. By contrast, a significant positive correlation between volumes of CSP and septal tissue volumes in patients with schizophrenia (P = 0.03) and in control cases (P < 0.01) was found, but not in patients with affective disorder (P = 0.53). The finding of enlarged CSP in schizophrenia strongly supports the hypothesis of an early developmental abnormality in this key structure of the limbic system.

Usefulness of Functional Image Analysis Using Positron Emission Tomography for the Discrimination between Hypoplastic Myelodysplastic Syndromes and Aplastic Anemia.

Myelodysplastic syndromes (MDS) and aplastic anemia (AA) are classified bone marrow failure syndromes. Their clinical and pathological features partly overlap. It is sometimes difficult to distinguish hypoplastic MDS from AA by using current common diagnostic methods such as bone marrow biopsy and chromosome analysis. Although magnetic resonance image (MRI) is useful for diagnosis of MDS with hypercellular bone marrow, it is difficult to discriminate between hypoplastic MDS and AA using this method because the high intensity patterns on T1-enhanced images are similar in these disorders. Quantitative imaging with fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been recognized as a useful examination for discrimination between benign and malignant regions in various conditions. Since the decrease in FDG uptake at the late phase is much slower in a malignant region than in a benign region, dual time point imaging provides more accurate information than does conventional single time point scanning. In this study, we investigated the usefulness of dual time protocol FDG-PET in differential diagnosis of hypoplastic MDS and AA. Seventeen patients (7 with typical MDS (RA), 4 with hypoplastic MDS, 6 with AA) and 30 healthy adults agreed to participate in this study. Bone marrow biopsy, FDG-PET, MRI and CT were carried out. Spine, femur and iliac lesions were detected by their increased FDG uptake at 60 and 120 min after injection of 0.12 mCi/kg of FDG. The mean lesional standardized uptake values (SUVmean) at 60 and 120 min after injection of FDG were determined. While the median SUVmean of normal lumbar regions at 60 min was 1.123 ± 0.219, that of MDS cases was 2.06 (range, 1.62–2.32). At 120 min, the median SUVmean of normal cases was 1.180 ± 0.119, whereas that of MDS cases was 2.44 (range, 2.08–2.98). It is noteworthy that the SUVmean of four hypoplastic MDS cases was also high (ranges: 1.96–2.23 at 60 min and 1.97–2.52 at 120 min), suggesting that bone marrow in hypoplastic MDS has a hyper-metabolic state of glucose like other malignant disorders. We also observed a patchy hot area, which may be a visualization of ineffective hematopoiesis, throughout the spine image of hypoplastic MDS. In contrast, the SUVmeans at both time points of four AA cases were not different from those in normal control cases. These results suggest that functional imaging analysis using an FDG-PET dual time protocol enables discrimination between hypoplastic MDS and AA, in which MR images similar intensities.

Hearing screening in infants with congenital cytomegalovirus infection

To investigate the impact of congenital cytomegalovirus infection on the hearing ability in infants. By using the tools of distortion product otoacoustic emission (DPOAE) and auditory brain-stem response (ABR), the hearing ability of 38 infants with congenital cytomegalovirus infection and 16 cases of normal controls during neonatal periods was screened with a follow-up study at 6 and 24 months. In infants with congenital cytomegalovirus infection, 86.8% (66/76) ears at neonatal stage and 76.3% (58/76) ears at 6 months passed the tests; while in normal controls, 96.9% (31/32) ears passed the tests. The reaction threshold of ABR V in infants with congenital cytomegalovirus infection was higher than that in normal controls (P<0.005). Furthermore,in infants with congenital cytomegalovirus infection, 13 ears (17.1%) were extreme hearing loss, 5 ears (6.6%) were severe hearing loss, and 6 ears (7.9%) were moderately severe hearing loss. The incidence of hearing loss during the follow-up was 7.9% (3/38) at neonatal stage, 23.7% (9/38) at 3-4 months, and 7.9% (3/38) after 6 months. The congenital cytomegalovirus infection could cause the prompt and late-onset hearing loss. The combination of the laboratory evidence with the dynamic hearing screening may contribute to the early detection of hearing loss in infants with congenital cytomegalovirus infection.

MTHFRC677T Polymorphism and Factor V Leiden Mutation Are Not Associated with Recurrent Spontaneous Abortion of Unexplained Etiology in Japanese Women

To determine whether the C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene and the Leiden mutation of coagulation factor V (FV) are associated with recurrent spontaneous abortion (RSA) of unexplained etiology in Japanese participants, the genotypes of the two polymorphisms were determined and compared between cases of unexplained RSA and normal pregnant controls. Eighty-three Japanese participants, consisting of 45 women with explained RSA and 38 women with unexplained RSA, and 174 controls were recruited in the study. The frequencies of the T677 allele/TT genotype were not significantly different among women with explained RSA (35.6%/13.3%), women with unexplained RSA (34.2%/7.9%), primigravid controls (35.1%/11.7%), and multigravid controls (39.7%/16.5%). In the cases of unexplained RSA, the frequencies of the T677 allele and TT genotype tended to increase according to the number of previous spontaneous abortions, but the increase was without statistical significance: the frequencies of the T677 allele and TT genotype in women with two abortions were 18.2% and 0%, whereas in women with three abortions the frequencies were 38.0% and 9.5%, and in women with four or more abortions the frequencies were 50.0% and 16.7%, respectively. In addition, no Leiden mutation of FV was detected in the women with RSA or the controls. Neither T677 of the MTHFR nor the Leiden mutation of FV was associated with unexplained RSA in the Japanese population.

Expression of Laminin and Fibronectin in Renal Dysplasia

The pathogenesis of renal dysplasia is a matter of debate. Recent theories have conceptualized the role of extracellular matrix proteins in the genesis of renal dysplasia. During normal nephrogenesis, collagen type I and III and fibronectins are lost and laminin and syndecan appear once proper induction has occurred. Any deviation from the normal pattern is said to lead to dysplasia. In this study, the expressions of adhesive glycoproteins, laminin, and fibronectin were studied immunohistochemically in 25 autopsy cases of renal dysplasia and normal age-matched control cases. These cases of renal dysplasia were categorized into 3 groups based on the period of gestation: 20 to 26 weeks, 27 to 33 weeks, and 34 to 40 weeks. The immunohistochemical findings were graded from 0 to 4+ based on the visual intensity. Chi-square analysis was used to calculate the difference in expressions of laminin and fibronectin in cases and controls as a whole and within and between age groups. Immunostaining for laminin in all age groups showed a significant difference in expression between dysplastic kidneys (less expression) and normal controls (greater expression). In the case of fibronectin expression, all but 1 group showed a significant difference, with dysplastic kidneys showing more and normal controls showing less expression. The inference derived is that laminin expression decreases and fibronectin expression increases in renal dysplasia compared with normal nephrogenesis.

Downregulation of Protein Phosphatase 2A Carboxyl Methylation and Methyltransferase May Contribute to Alzheimer Disease Pathogenesis

ABalphaC, a major protein phosphatase 2A (PP2A) heterotrimeric enzyme, binds to and regulates the microtubule cytoskeleton and tau. We have shown that ABalphaC protein expression levels are selectively reduced in Alzheimer disease (AD). Notably, the carboxyl methylation of PP2A catalytic subunit (PP2A(C)) is critically required for ABalphaC holoenzyme assembly, and catalyzed by a specific methyltransferase (PPMT). Here, we provide the first analysis of human PPMT and methylated PP2A(C) in brain regions from AD, non-AD demented, and aged control autopsy cases. Immunoblotting analyses revealed that PPMT protein expression and PP2A(C) methylation levels were quantitatively decreased in AD-affected brain regions. Immunohistochemical studies showed that PPMT was abundant in neurons throughout the cortex in normal control and non-AD demented cases. However, in AD, there was a regional loss of PPMT immunoreactivity that closely paralleled the severity of tau pathology, but not amyloid plaque burden. We propose that the deregulation of PPMT and PP2A methylation/demethylation cycles contributes to AD pathogenesis, by inducing changes in PP2A heteromultimeric composition and substrate specificity. In turn, PP2A dysfunction compromises the mechanisms that control tau, neuronal plasticity, and survival.