Biomedical subjects

B Sablonnière

Publications and source records attributed to B Sablonnière.

At least 19 recordsLinked to original sources

PubMed2004

GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene.

A maternally inherited and practically homoplasmic mitochondrial (mtDNA) mutation, 8527A>G, changing the initiation codon AUG into GUG, normally coding for a valine, was observed in the ATP6 gene encoding the ATPase subunit a. No alternate Met codon could replace the normal translational initiator. The patient harboring this mutation exhibited clinical symptoms suggesting a mitochondrial disease but his mother who carried the same mtDNA mutation was healthy. The mutation was absent from 100 controls and occurred once amongst 44 patients suspected of Leber Hereditary Optic Neuropathy (LHON) but devoid of typical LHON mutations. In patient fibroblasts, no effect of 8527A>G mutation could be demonstrated on the biosynthesis of mtDNA-encoded proteins, on size and the content of ATPase subunit a, on ATP hydrolysis and on mitochondrial membrane potential. In addition, ATP synthesis was barely decreased. Therefore, GUG is a functional initiation codon for the human ATP6 gene.

Adenosine Triphosphatases↗

PubMed2001

Real time RT-PCR shows correlation between retinoid-induced apoptosis and NGF-R mRNA levels.

Neurotrophins and retinoic acid have a critical role in the differentiation and the survival of neurons. All-trans-, 9-cis-retinoic acid (10(-6) M) or NGF (50-100 ng/ml) induced morphologic differentiation and inhibited cell growth in SH-SY5Y neuroblastoma cells after 7 days of culture. Continuous treatment of undifferentiated cells with all-trans- or 9-cis-retinoic (10(-6) M) did not induce apoptosis, whereas NGF-differentiated cells showed dramatic apoptosis after 2 to 4 days of retinoic acid treatment as evidenced by TUNEL reaction and flow cytometry analysis following propidium iodide staining. Addition of Ro41-5253 blocked all-trans-retinoic-induced apoptosis, suggesting that the apoptotic signaling pathway was mediated by RARs. The effects of all-trans- or 9-cis-retinoic acid on the expression of NGF receptors was evaluated using real-time fluorescence reverse transcription-PCR. A slight transient increase in the expression of p75(NGFR) mRNA was observed by 2 to 4 h after retinoid treatment of undifferentiated cells, whereas a larger increase in the expression of both TrkA and p75(NGFR) mRNA up to threefold the basal level, was observed by 2 to 6 h after retinoid treatment of NGF-differentiated cells. Our results suggest that NGF-differentiated cells may be more susceptible to retinoid-induced apoptosis than undifferentiated cells.

Alitretinoin↗

PubMed2001

Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1.

Intraneuronal aggregates of hyperphosphorylated tau proteins, referred to as pathological tau, are found in brain areas of demented patients affected by numerous different neurodegenerative disorders. We previously described a particular biochemical profile of pathological tau proteins in myotonic dystrophy type 1 (DM1). This multisystemic disorder is characterized by an unstable CTG repeat expansion in the 3'-untranslated region of the DM protein kinase gene. In the human central nervous system, tau proteins consist of six isoforms that differ by the presence or absence of the alternatively spliced exons 2, 3 and 10. Here we show that the pattern of tau isoforms aggregated in DM1 brain lesions is characteristic. It consists mainly of the aggregation of the shortest human tau isoform. A disruption in normal tau isoform expression consisting of a reduced expression of tau isoforms containing the exon 2 was observed at both the mRNA and protein levels. Large expanded CTG repeats were detected and showed marked somatic heterogeneity between DM1 cases and in cortical brains regions analysed. Our data suggest a relationship between the CTG repeat expansion and the alteration of tau expression showing that DM1 is a peculiar tauopathy.

Adult↗

PubMed2001

Clinical features and genetic analysis of a new form of spinocerebellar ataxia.

BACKGROUND: The autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of disorders. The mutations for SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, and SCA-12 are identified and caused by an expansion of a CAG or a CTG repeat sequence of these genes. Six additional loci for SCA4, SCA5, SCA-10, SCA-11, SCA-13, and SCA-14 are mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic etiologies of at least 20% of ADCA have yet to be elucidated. METHODS: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant phenotype for SCA. Direct mutation analysis, repeat expansion detection analysis, and linkage analysis for all known SCA loci were performed. RESULTS: Direct mutational analysis excluded SCA1, 2, 3, 6, 7, 8, and 12; genetic linkage analysis excluded SCA4, 5,10, 11, 13, and 14, giving significant negative lod scores. Examination of the family showed that all affected members had gait ataxia and akinesia with variable features of dysarthria, hyporeflexia, and mild intellectual impairment. Eye movements were normal. Head MRI showed atrophy of the cerebellum without involvement of the brainstem. In 10 parent-child pairs, median onset occurred 10.5 years earlier in offspring than in their parents, suggesting anticipation. CONCLUSION: This family is distinct from other families with SCA and is characterized by cerebellar ataxia and extrapyramidal signs.

Adult↗

PubMed2000

Symptomatic hyperlactataemia: an emerging complication of antiretroviral therapy.

BACKGROUND: Fatal lactic acidosis is a serious complication of therapy with nucleoside analogues. OBJECTIVE: To examine symptomatic hyperlactataemia in HIV-infected adults treated with antiretroviral drugs. METHODS: In this prospective study, arterial blood lactate levels were measured in patients presenting with unexplained clinical symptoms. When these levels were high, functional respiratory tests (FRT) were carried out. Liver or muscle biopsies were further proposed. Incidences were calculated by comparison with the entire cohort of patients treated in the department. RESULTS: Fourteen HIV-infected adults treated with antiretroviral drugs were identified with symptomatic hyperlactataemia during a 2-year period follow-up study. The incidence of hyperlactataemia was 0.8% per year but reached 1.2% if only patients treated with a regimen including stavudine were considered. Clinical symptoms included abnormal fatigue, tachycardia, abdominal pain, weight loss, peripheral neuropathy, and more specifically exercise-induced dyspnoea occurring despite effective antiretroviral treatment. FRT showed a metabolic deviation towards anaerobiosis with a high lactate/pyruvate ratio. Ultrastructural mitochondrial abnormalities were seen in all four patients for whom this was examined. There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction. Evolution was favourable in 13 patients, probably because of an early diagnosis. CONCLUSIONS: Potentially fatal adverse events occurring during antiretroviral treatment may be avoided by close monitoring of clinical signs and blood lactate levels. If other studies confirm that the cumulative long-term toxicity of antiretroviral drugs results from mitochondrial dysfunction, the incidence of hyperlactataemia and its clinical consequences may become more important.

Acidosis, Lactic↗

PubMed2000

Critical role of tyrosine 277 in the ligand-binding and transactivating properties of retinoic acid receptor alpha.

Retinoic acid receptors specifically bind all-trans-retinoic acid (RA) and function as RA-inducible transcriptional regulatory factors. Binding of RA to RARalpha, beta, and gamma is sensitive to nitration with tetranitromethane, a tyrosine-specific modifying reagent. To identify tyrosine residue(s) that are important for RA binding, we carried out chemical modification experiments with purified RARalpha ligand-binding domain (RARalpha-LBD) subjected to partial acid hydrolysis and selective proteolysis. The chemically modified peptides containing each of the three Tyr residues present in the RARalpha-LBD sequence were then analyzed and identified by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC/ESI-MS). We found that RA binding to RARalpha-LBD protected Tyr(277)-containing peptides from nitration. Protection of Tyr(277) could result either from direct masking by the bound ligand or from ligand-induced changes in receptor conformation and tyrosine accessibility. The role of Tyr residues was further documented by site directed mutagenesis using three site-specific RARalpha mutants: Y208A, Y277A, and Y362A. The affinity for RA of these mutant receptors was in the range of that of the wild-type protein, except for the Y277A receptor mutant, which displays a 15-20-fold reduction in affinity and transactivation activity for RA. Whereas mutation of Tyr(277) into alanine had a variable effect on different agonists and antagonists binding, it caused a dramatic decrease of retinoid-dependent transactivation activity. This later effect was also observed with mutation of Tyr(277) into phenylalanine. It is unlikely that major conformational changes are responsible for the lower affinity of RA binding and RA-dependent transactivation since these mutants displayed wild-type dimerization and DNA-binding activities. Limited proteolysis revealed that upon ligand binding, the Y277A mutant induced a conformational change slightly different from that obtained with the wild-type protein. These data could suggest that Tyr(277) play a critical role in the ligand-induced conformational changes required for the activation of RARalpha.

Alanine↗

PubMed2000

The first identified French family with dentatorubral-pallidoluysian atrophy.

We report the first French family with dentatorubral-pallidoluysian atrophy (DRPLA) in which three members, a 36-year-old woman (proband), her 34-year-old sister, and 14-year-old brother were affected. There was no family history of DRPLA and their father presented at age 66 with pes cavus but without any other neurologic symptoms. Molecular analysis of the DRPLA gene from blood leukocytes showed CAG repeat sizes to be 68/16 in the proband, 62/15 in her father, and 16/16 in her mother. This study provides support for the variable clinical presentation of this disease with incomplete penetrance in the father and demonstrates that DRPLA can be observed in the French Caucasian population.

Adult↗

PubMed2000

Absence of unidentified CAG repeat expansion in patients with Huntington's disease-like phenotype.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded (CAG)n repeat on the huntingtin gene. It is characterised by motor, psychiatric and cognitive disturbances. Diagnosis can be confirmed by direct genetic testing, which is highly sensitive and specific and is now considered definitive. This study focused on 21 patients presenting with a clinical phenotype showing strong similarity to HD, but who do not have an expanded CAG in the huntingtin gene. However, other possible diagnoses could be evoked for most of them. Seven patients (3.5% of our cohort) could be considered as phenocopies of HD with no alternative diagnosis. Samples were screened for other triplet repeat diseases with similar presentation (DRPLA, SCA-1, SCA-2, SCA-3, SCA-6, and SCA-7) and were all negative. The repeat expansion detection technique (RED) was used to detect uncloned CAG repeat expansions and samples were also analysed by polymerase chain reaction for expansions of the polymorphic CAG-ERDA-1 and CTG18.1 trinucleotide repeats. RED expansion (>40 repeats) was detected in only one patient. The results suggest that unstable CAG/CTG repeat expansions corresponding to known or unknown sequences are not involved in the aetiology of HD-like disorders. It is hypothesised that some of these phenocopies could correspond to mutations in other unidentified genes with other unstable repeats (different from CAG) or in unknown genes with other mutations.

Adult↗

PubMed2000

Cyclin-dependent kinase inhibitory protein expression in human choroidal melanoma tumors.

PURPOSE: Recent studies have demonstrated the close link between oncogenesis and cell cycle machinery. Cyclin-dependent kinase inhibitory proteins (CKIs) have been shown to play a critical role in the regulation of cell cycle progression. Alteration of CKI levels and/or functions could be implicated in cell transformation. The three CKIs-p16, p21, and p27-were investigated in human uveal melanoma tumors, and an attempt was made to correlate their levels with clinicopathologic parameters, as well as to p53 and Ki-67 (Mib-1) protein levels. METHODS: Immunochemistry was performed on 32 formalin-fixed, paraffin-embedded specimens of malignant choroidal melanoma. Immunoblot was performed to confirm the immunochemistry study. Prognostic histologic markers such as cell typing, pigmentation, larger tumor dimension, mitotic figures, nucleolar size, scleral invasion, and optic nerve head invasion were reported. RESULTS: Nuclear positivity for p16 was observed in 11 tumors (34%) without any association with clinicopathologic parameters. Tumor cells positive for p21 were detected in 12 choroidal melanomas (37%). Unexpectedly, a positive relationship was seen between p21 and scleral invasion (P: = 0.008). Nuclear positivity for p27 was observed in nine tumors (28%). An inverse correlation was observed between the number of mitotic figures and p27 immunoreactivity (P: = 0.03), as well as between Mib-1 positivity and p27 expression (P: = 0.02). Western blot assays of tumor extracts confirmed overexpression of p21 and p27. CONCLUSIONS: The results suggest that p21 and p27 may be involved in tumorigenesis in choroidal melanoma.

Adult↗

PubMed1999

Analysis of ERDA1, CTG18.1, and uncloned CAG/CTG repeat sequences in familial Parkinson's disease with anticipation.

In several neurodegenerative diseases, anticipation or increase in disease severity in succeeding generations within families correlates with expansions of an intragenic CAG/CTG repeat sequence above the normal range through the generations of a pedigree. Some kindreds of familial Parkinson's disease (PD) exhibit genetic anticipation. We used the repeat expansion detection (RED) method to detect repeat expansions directly in DNA samples from the index cases of 34 different PD families with anticipation. The mean age at onset of the younger probands was 48.8 +/- 10.8 years and the mean intergenerational difference was 19.2 +/- 10 years. The distribution of the RED products greater than 40 repeats was not significantly different between patients and controls with the Mann-Whitney U test (U = 510.5, p = 0.67). The samples were then screened for the two expanded-repeat loci, ERDA1 and CTG18.1. We found that in all cases the repeat expansion detected by the RED method may be accounted for by an expansion at these loci. Our results demonstrate that unstable CAG/CTG expansions corresponding to uncloned or cloned sequences (ERDA1, CTG18.1) are not involved in the etiology of rare familial case of PD with genetic anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:738-741, 1999

Adult↗

PubMed1999

[Genetic dystonia].

A NEW CLASSIFICATION: The advent of molecular genetics has led to a total revision of earlier classifications of primary dystonias. LOCUS DYT-1 PRIMARY DYSTONIA: Locus DYT1, situated on chromosome 9, is responsible for the most common phenotypic expression of generalized primary dystonia, Ziehen-Oppenheim disease. This autosomal dominant disease has variable penetration. It has long been recognized that some individuals in families with typical disease only have segmentary, multifocal or even focal dystonia. It has been proven by molecular genetics that the disease can be expressed simply by familial writers cramp with particularly early, and often bilateral, onset. The mutation concerns the torsine A gene, whose function remains to be elucidated. Torsine A is found in the central nervous system, particularly in the dopaminergic neurons of the locus niger. GENERALIZED PRIMARY DYSTONIA UNRELATED TO DYT-1: These dystonias are phenotypically different: younger and more variable age at onset, focal localization early in the disease course generally involving the cervical or cephalic pole, less severe course. Certain forms are linked to chromosome 8 (locus DYT 6). PRIMARY FOCAL OR SEGMENTARY DYSTONIAS: These primary dystonias cause functional or postural disorders and were long considered as sporadic despite rare familial cases suggesting a genetic factor. When searched for systematically, familial cases are found in 20 to 30% of the cases. The dystonia is transmitted by dominant autosomal heredity with reduced penetration. Phenotypically, expression is heterogeneous with a constant frequency of unrecognized or neglected forms and of postural forms. One form is known to be linked to chromosome 18 (locus DYT 7). DOPA-RESPONSIVE DYSTONIA: This class represents 5 to 10% of childhood dystonias. The phenotypic expression is polymorphous but symptoms always improve with very small doses of L-dopa. Both sporadic, and more frequently familial, cases are described. Some forms are recessive, caused by mutation of the gene coding for tyrosine hydroxylase, others are autosomal dominant, often linked to mutation of the gene coding for GTP cyclohydrolase. RAPID ONSET DYSTONIA SYNDROME-PARKINSONISM: This dominant autosomal dystonia is quite exceptional, ... and intriguing.

Adolescent↗

PubMed1998

Simple nonisotopic assays for detection of (CAG)n repeats expansions associated with seven neurodegenerative disorders.

To date, eight neurodegenerative diseases, including Huntington's disease, dentatorubral-pallidoluysian atrophy, spinal and bulbar muscular atrophy, and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7, have been proven to be caused by an expanded trinucleotide repeat (CAG)n located within a specific gene for each of these diseases. Except in SCA 6, the CAG repeat is present in approximately 7 to 35 copies in the normal population, whereas patients have CAG expansions of 40 to approximately 75 repeats. Sizing of the repeat length enables molecular diagnosis in affected patients and presymptomatic persons carrying a mutated allele. A molecular protocol for the diagnosis of these diseases was developed based on polymerase chain reaction, denaturing polyacrylamide gel electrophoresis and staining with silver nitrate, and adapted to each disease. This simple and rapid method gives a sensitivity of detection equal to current procedures but avoids isotopic manipulations. Therefore, shorter turnaround time, decreased cost per sample, and simplified screening of these neurodegenerative diseases by PCR-based assays may be attainable using this protocol.

DNA↗

PubMed1998

Genetic polymorphisms adjacent to the CAG repeat influence clinical features at onset in Huntington's disease.

OBJECTIVES: To evaluate possible influences of CCG and delta2642 glutamic acid polymorphisms adjacent to the (CAG)n trinucleotide repeat in Huntington's disease gene IT15 on some clinical features (age and symptoms) at onset. METHODS: 84 patients and a control group of 68 unaffected relatives were studied. Patients all belonged to a group of affected persons tested for molecular confirmation of Huntington's disease. The length of the CAG repeat sequence in the IT15 gene and the adjacent CCG and delta2642 polymorphisms were determined by quantitative polymerase chain reaction. RESULTS: Two intragenic polymorphisms were studied: (CCG)n and delta2642 glutamic acid. Patients were classified firstly according to the size of the CCG rich segment adjacent to the CAG repeat into genotype groups CCG 7/7, 7/8, 7/9, 7/10, and 10/10 and then according to delta2642 polymorphism into genotype groups A/A (absence of the delta2642 deletion), A/B, and B/B (presence of the delta2642 deletion in respectively one and two alleles). The presence of delta2642 mutation was associated with a significant decrease in age at onset, although there was no significant increase in CAG size. A good correlation was found between the (CAG)n trinucleotide repeat size and the age at onset in patients with genotype AA (r2=0.72). Within patients of the A/B genotype group however, a significant correlation was found but with a drop of the r2 value to 0.44. No association was found between age at onset and the CCG polymorphism. Although an increased percentage of patients within the A/A genotype group had a neurological onset, we found no overall significant association between CCG or delta2642 polymorphisms and the nature of symptoms at onset. CONCLUSIONS: The delta2642 glutamic acid polymorphism did not affect CAG repeat size nor the nature of symptoms at onset but seems to influence the age at onset in patients with Huntington's disease.

Adenine↗

PubMed1998

The first European family with tibial muscular dystrophy outside the Finnish population.

We report the first European tibial muscular dystrophy (TMD) family outside the Finnish population. Clinical examination showed late onset distal leg myopathy similar to the description of TMD. A molecular genetic study was made owing to the very recent TMD linkage findings on chromosome 2q31. All five clinically affected patients segregated a specific haplotype for the locus, whereas two unaffected patients had different haplotype. The results of this family without Finnish ancestors show that TMD exists outside the Finnish population.

Aged↗

PubMed1994

Physicochemical parameters affecting the charcoal adsorption assay for quantitative retinoid-binding measurement.

The different parameters affecting the accuracy and reliability of the dextran-coated charcoal adsorption assay for characterization of retinoic acid receptors ligand binding activity were investigated. Using dextran-coated charcoal (DCC) at a final 10 mg/ml concentration, an efficient adsorption of free [3H]retinoic acid was observed with a yield in the range 99.2 to 99.8% for ligand concentrations varying from 10(-9) to 10(-4) M. Nonspecific adsorption of retinoic acid reached 50% to polystyrene and silanized glass and 70% to uncoated glass. Results obtained by the DCC method and by gel-filtration assay were correlated; however, the DCC assay appeared easier to perform and gave more reproducible results. When a careful measurement of free retinoid concentration was performed, the apparent equilibrium dissociation constant (KD) of retinoic acid was 3.1 +/- 0.4 nM and the KD of CD367, a synthetic retinoid, was 1.8 +/- 0.3 nM. Optimal pH for the binding of [3H]retinoic acid or [3H]CD367 was in the range 7.5 to 8.5. Under the conditions described for the adsorption assay, bound retinoid measurement was linearly related to the protein concentration between 0.05 and 0.25 mg/ml. At a lower protein concentration, addition of bovine serum albumin exerted a stabilizing effect on retinoid binding, allowing an accurate measurement of the number of specific binding sites. Using retinoic acid as ligand, bacterial extracts often resulted in a level of nonspecific binding in the range 10-25%. It could be lowered (4-10%) when resorting to [3H]CD367.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

PubMed1993

Purification and functional characterization of the ligand-binding domain from the retinoic acid receptor alpha: evidence that sulfhydryl groups are involved in ligand-receptor interactions.

The pGEX-2T expression vector was used to produce the ligand-binding domain from the human retinoic acid receptor alpha (hRAR alpha LBD) in Escherichia coli. The resulting fusion protein, containing the glutathione S-transferase separated from the truncated receptor (hRAR alpha 186-462) by a thrombin cleavage site, was purified with use of affinity chromatography on immobilized glutathione. A 90% homogeneity was obtained, with a specific activity of 100 pmol/mg and an overall 10% yield. Following purification and thrombin cleavage, a predominant monomeric (stokes radius = 2.3 nm, molecular mass of 32 kDa) [3H]retinoic acid hRAR alpha LBD complex was characterized by high-performance size-exclusion chromatography. The purified hRAR alpha LBD bound retinoic acid with an apparent Kd of 9 nM, a value close to the Kd of the full-length hRAR alpha expressed in COS cells. Kinetic studies at 0 degrees C demonstrate that the association of [3H]retinoic acid and [3H]CD367, a synthetic retinoid, to the overexpressed receptor was extremely rapid (complete in less than 3 min), whereas their dissociation from the receptor was slower, with half-lives of about 40 min at 0 degrees C. Experiments performed at various subzero temperatures allowed a more accurate assay of the association rate constant and indicate that the entropy of activation (delta Sa) is positive, which is characteristic of hydrophobic interactions. The ligand-binding activity was markedly decreased by pretreatment with various sulfhydryl modifying agents. 5,5'-Dithiobis(2-nitrobenzoic acid) (DTNB) appeared to be the most potent, whereas iodoacetamide was the least active. Furthermore, a series of N-alkylmaleimides was shown to inactivate the recombinant receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

PubMed1992

Synthesis of a biospecific adsorbent for the purification of the three human retinoic acid receptors by affinity chromatography.

The total synthesis of an affinity gel suitable for the purification of retinoic acid receptors (hRARs) is reported. A chalcone derived from a potent retinobenzoic acid (Ch55) was chosen as the ligand and fixed to an immobilized matrix by coupling with the N-hydroxysuccinimide ester of agarose (Affi-Gel 10, Bio-Rad Laboratories). Efficiencies of purification of the different human RARs were tested, using recombinant receptors produced with the baculovirus expression system.

Carrier Proteins↗

PubMed1990

Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins.

Bundles of paired helical filaments (PHF) accumulate in the pyramidal neurons that degenerate during Alzheimer's disease. This neurofibrillary degeneration is highly correlated with clinical signs of dementia. During the degenerating process, Tau proteins, which are the major antigenic components of PHF, are abnormally phosphorylated and two pathological isoforms named Tau 64 and 69 are expressed. We have studied their immunoblot distribution in the cortical gray and white matter from different regions of normal and Alzheimer brains, to determine if the degenerating process preferentially affects the somatodendritic or the axonal domain. Two categories of antibodies were used. The first category consisted of anti-human native Tau, anti-Tau proteins from different vertebrates, anti-PHF, monoclonal antibody Alz-50 and an anti-C terminal repeated region of Tau. In control brains, these antibodies strongly detected normal Tau proteins in the gray matter while Tau immunodetection was weak in the white matter. In Alzheimer brain cortices, each antibody detected Tau 64 and 69 in gray matter extracts but not at all in white matter extracts. The second category of anti-Tau consisted of the anti-PHF saturated with normal brain protein extracts. This antiserum only probed the abnormally phosphorylated Tau proteins. It detected Tau 64 and 69 exclusively in the cortical gray matter of Alzheimer brains. Moreover, a 55-kDa Tau protein was also immunolabelled, which might be an intermediary form between normal Tau and Tau 64 and 69. Our results demonstrate that Tau proteins are normal and major components of the somatodendritic domain and that Tau pathology, reflected by the presence of Tau 64 and 69, affects preferentially this domain during Alzheimer's disease.

Aged↗