Jordi Pérez-Tur - Academia.edu (original) (raw)
Papers by Jordi Pérez-Tur
Epilepsy Research, 2006
Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADL... more Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the A. 3 identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both
Revista de neurologia
With their discovery in 1995, presenilins were put forward as molecules of unknown function but c... more With their discovery in 1995, presenilins were put forward as molecules of unknown function but central to the aetiology of Alzheimer s disease. The fact that point and splice mutations lead to an increase in the amount of Ab peptide produced by the cells, provided further support for the amyloid theory about the origin of the disease and, on the other hand, placed these molecules in the central part of this theory. Different groups showed that these proteins had also roles in several cellular pathways, among those, the notch pathway is one of the most important, as it is with the interaction among presenilin 1 and b catenin. Recently, several works have suggested that presenilins are molecules involved in the processing of APP by being an integral part of the protein complex that process the precursor to produce the amyloid peptide. In this paper, I will give an overview of some of the most recent work developed towards the identification of presenilin function and its involvement ...
Nature neuroscience, 1998
Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and relate... more Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and related dementias. Here we review genetic and molecular biological evidence suggesting that the peptide A beta 42 is central to the etiology of AD. Recent data also suggests that dysfunction in the cytoskeletal protein tau is on the pathway that leads to neurodegeneration and dementia. Tau is produced either indirectly, by A beta 42, or directly, in some forms of frontotemporal dementia by mutations in tau itself. These data support are refine the amyloid cascade hypothesis for AD and suggest that understanding the causes and consequences of tau dysfunction is an important priority for dementia research.
Down's syndrome (DS) patients develop the characteristic features of Alzheimer's disease (AD) by ... more Down's syndrome (DS) patients develop the characteristic features of Alzheimer's disease (AD) by their fourth decade, some of them exhibiting an AD-type dementia. We studied the apolipoprotein E (APOE) allele distribution in a population of 41 DS patients comprising 19.5% of demented, compared to 35 control subjects. No statistical difference was observed, but the e2 allele may delay the age of dementia. As described in other studies, the impact of the different APOE alleles in DS is modest. However the compilation of all published studies on AD-type dementia in DS suggests that the e2 allele has a protective effect. In delaying the age of onset, the E2 allele would have a similar action in AD-type dementia in DS and in AD families with amyloid precursor protein (APP) mutations.
Virchows Archiv, 2003
Loss of heterozygosity in the long arm of chromosome 10q is a frequent event in gliomas. It may i... more Loss of heterozygosity in the long arm of chromosome 10q is a frequent event in gliomas. It may involve the LGI1/epitempin gene, which is located in chromosomal region 10q23 approximately 24 and has been proposed to encode a tumor suppressor inactivated in the progression of brain tumors. Nevertheless, so far no data are available demonstrating that the reduced expression of the LGI1 transcript in high-grade astrocytic tumors indeed results in a decreased level of LGI1 protein in the tumor cells. Thus, the aim of the present study was to analyze the expression of the LGI1 protein in a series (ten of each) of pilocytic astrocytomas, astrocytomas [World Health Organization (WHO) grade II], anaplastic astrocytomas (WHO grade III), and glioblastoma multiforme (WHO grade IV). Immunohistochemistry demonstrated a strong expression of the LGI1 protein in normal brain tissue as well as in the majority of pilocytic astrocytomas and astrocytomas (WHO grade II). In anaplastic astrocytomas, the number of tumor cells expressing LGI1 decreased, while LGI1 expression was completely absent from the glioblastomas of this series. This highly significant reduction of LGI1 protein expression in the progression of astrocytic brain tumors lends further support to the hypothesized function of LGI1 as a type-II tumor suppressor gene in glioma pathogenesis.
Trends in Biochemical Sciences, 2002
Recent studies suggest that mutations in the LGI1/Epitempin gene cause autosomal dominant lateral... more Recent studies suggest that mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal epilepsy. This gene encodes a protein of unknown function, which we postulate is secreted. The LGI1 protein has leucine-rich repeats in the N-terminal sequence and a tandem repeat (which we named EPTP) in its C-terminal region. A redefinition of the C-terminal repeat and the application of sensitive sequence analysis methods enabled us to define a new superfamily of proteins carrying varying numbers of the novel EPTP repeats in combination with various extracellular domains. Genes encoding proteins of this family are located in genomic regions associated with epilepsy and other neurological disorders.
Revue Neurologique, 2010
f unit of Molecular genetics, Biomedical institute, valencia, espagne g uSTl, Département des Neu... more f unit of Molecular genetics, Biomedical institute, valencia, espagne g uSTl, Département des Neurosciences, villeneuve d'Ascq, France
Psychiatric Genetics, 2006
A mutation in the FOXP2 gene has been the first genetic association with a language disorder. Lan... more A mutation in the FOXP2 gene has been the first genetic association with a language disorder. Language disorder is considered as a core symptom of schizophrenia. Therefore, the FOXP2 gene could be considered a good candidate gene for the vulnerability to schizophrenia. A set of single nucleotide polymorphisms mainly located in the 5' regulatory region of the FOXP2 gene was analysed in a sample of 186 DSM-IV schizophrenic patients with auditory hallucinations and in 160 healthy controls. Statistically significant differences in the genotype (P=0.007) and allele frequencies (P=0.0027) between schizophrenic patients with auditory hallucinations and controls were found in the single nucleotide polymorphism rs2396753. These P values changed to 0.07 and 0.0273, respectively, after Bonferroni sequential correction. The haplotype rs7803667T/rs10447760C/rs923875A/rs1358278A/rs2396753A (TCAAA) also showed a significant difference confirmed with a permutation test (P=0.009). These results suggested that the FOXP2 gene may confer vulnerability to schizophrenic patients with auditory hallucinations.
Parkinsonism & Related Disorders, 2013
Neuroscience Letters, 1999
In a series of sibpairs with late onset Alzheimer's disease, we have examined the segregation of ... more In a series of sibpairs with late onset Alzheimer's disease, we have examined the segregation of the loci involved in the early onset, autosomal dominant form of the disorder by using¯anking microsatellite repeat markers: thus we have used APP-PCR3 and D21S210 to examine the segregation of the amyloid-b precursor protein (APP) gene, the markers Dl 4S77 and D14S284 to examine the segregation of the presenilin 1 (PSI) gene and the markers D1S227, D1S249 and D1S419 to examine the segregation of presenilin 2 (PS2). We carried out our analyses on the whole dataset of 291 affected sibpairs, and on subsets comprising those sibpairs in which neither had an apolipoprotein E4 allele (65 affected sibpairs) and those in which both had an apolipoprotein E4 allele (165 affected sibpairs). We used the programs SPLINK to generate allele frequencies and MAPMAKER/SIBS to analyze our results. We examined the segregation of the markers D19S908 and D19S918 that are close to the apolipoprotein E (ApoE) gene as a positive control to assess whether the methods we are employing have the capability to identify known loci. The sibpair approach to the identi®cation of genetic risk loci is relatively insensitive as indicated by the failure of the ApoE locus to reach statistical signi®cance (P 0:06). Nevertheless, these data suggest that neither the PS1 nor the PS2 gene is a major locus for late-onset AD, but that the APP gene cannot be ruled out as a risk locus in those sibships without an E4 allele (P 0:014). The possibility that APP is indeed a locus for late onset disease will need con®rmation in other series of familial cases. q
Neuroscience Letters, 1997
Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people. ... more Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people. It usually occurs after 65 years old (late-onset AD). The e4 allele of apolipoprotein E (APOE) gene is a risk factor which contributes about 50% of the genetic risk for this form of the disease. The low density lipoprotein receptor-related protein (LRP) is a major receptor for APOE which is found in the senile plaques of AD brains. This makes it a good candidate gene for the disease. There is a polymorphism in the region upstream of the LRP gene that has been associated with AD in an American population. We examined this polymorphism by restriction fragment length polymorphism analysis in a French population with sporadic late-onset AD. In the previous report, a significant increase of the 87 bp allele was found in the AD cases; however, in our population, we observed a significant decrease with this same allele of the LRP gene. The possible reasons for this discrepancy, linkage disequilibrium or statistical anomaly, are discussed.
Neuroscience Letters, 1999
We have assessed whether apolipoprotein E (ApoE) genotype influences the age of onset of dementia... more We have assessed whether apolipoprotein E (ApoE) genotype influences the age of onset of dementia in a series of families with frontal temporal dementia with defined mutations in the tau gene. In contrast to the situation in Alzheimer's disease (AD), we could find no evidence that the age of onset of disease was influenced by the ApoE genotype.
Neuroscience Letters, 2000
Increasing evidence suggests a relation between vascular disorders and late-onset Alzheimer's dis... more Increasing evidence suggests a relation between vascular disorders and late-onset Alzheimer's disease (AD). We performed an association analysis of low-density lipoprotein receptor-related protein (LRP), lipoprotein lipase (LPL), and angiotensin converting enzyme (ACE) genes, known to be involved in vascular disorders, and AD. Genotyping was carried out in 113 patients with clinically de®ned Alzheimer's disease (NINCDS-ADRDA criteria) and 203 non-demented controls in a prospective, population-based study of people aged 85 years or over (Vantaa 851 Study). Corresponding analysis was performed on 121 neuropathologically veri®ed AD patients (CERAD criteria) and 75 controls derived from the same study population. We did not ®nd signi®cant associations between the polymorphisms studied and AD. However, analysis of the LPL polymorphism showed a weak trend (uncorrected P-value 0.095) towards protection against neuropathologically de®ned AD. Our study is based on very elderly Finns. Therefore, further studies are warranted in other populations. q
Neuroscience Letters, 1999
Using a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (... more Using a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing techniques, we identified a unique missence mutation (T → C) in exon 3 of the APOE gene which resulted in the substitution of pro-28 for leu-28. We screened 1118 White cases of late-onset (Ͼ60 years) Alzheimer's disease (AD) from three independent centers (Pittsburgh = 489, Indiana = 319, Mayo Clinic Rochester = 310) and 1123 controls (607 clinically assessed and 516 individuals randomly ascertained from the general population). Two of the 1123 control subjects had the pro-28 mutation (0.18%). However, this mutation was observed in heterozygous state in 2.66, 2.51 and 1.94% of the AD cases from Pittsburgh, Indiana and Mayo Clinic Rochester, respectively, with an overall frequency of 2.42%. All individuals with this mutation were carriers of the APOE*4 allele and hence the mutation was denoted as APOE*4 Pittsburgh (APOE*4P). Compared with the non-E*4P carriers, the E*4P carriers were associated with an increased risk of AD (odds ratio (OR) 13.2) and this risk remained significant even after adjusting for the known effect of APOE*4 (OR 5.4). The risk associated with the E*4P/E*4 combination was about five times (OR 29.1) the risk attributed to APOE*4 carriers alone (OR 5.7). Our data indicates that the new mutation most likely exists in cis-orientation with APOE*4 and is associated with increased risk of developing AD.
Neuroscience Letters, 1999
Recent reports have suggested that variability in the a2-macroglobulin gene is a genetic risk fac... more Recent reports have suggested that variability in the a2-macroglobulin gene is a genetic risk factor for Alzheimer's disease. Here we have both tested a common polymorphism in the gene (I1000V) for association with the disease in a four-site case control study design, and tested the locus for linkage in a large series of sibpairs afflicted with late onset disease. Our results fail to show an association between this polymorphism and disease.
Neuroscience Letters, 1991
A number of polyanions, including polysulfates (sulfated glycosaminoglycans (GAGs), dextran and p... more A number of polyanions, including polysulfates (sulfated glycosaminoglycans (GAGs), dextran and pentosan sulfates, and polyvinylsulfate), polyphosphates (tetrapolyphosphate, polyadenylate) and polycarboxylates (polyaspartate, polyglutamate) solubilize asymmetric acetylcholinesterase (AChE) from chick muscle at low ionic strength, and partially or totally displace AChE tailed forms bound to heparin-agarose columns. The previously reported solubilization of asymmetric AChE by heparin, or the proven affinity of the tailed enzyme forms for this GAG, cannot therefore be taken as direct proof of the involvement of heparin-like heparan sulfate proteoglycans in the anchorage of the collagenous tail of the enzyme to the basal lamina in skeletal muscle.
Neuroscience Letters, 2000
We and others have previously identi®ed two distinct haplotypes of the TAU gene in Caucasian popu... more We and others have previously identi®ed two distinct haplotypes of the TAU gene in Caucasian populations. In this study, we have assessed whether these haplotypes show an association with Alzheimer's disease in a variety of populations. They do not. These data are consistent with the view that the involvement of TAU in Alzheimer's disease is a downstream event. q (J. Hardy).
Epilepsy Research, 2006
Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADL... more Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the A. 3 identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both
Revista de neurologia
With their discovery in 1995, presenilins were put forward as molecules of unknown function but c... more With their discovery in 1995, presenilins were put forward as molecules of unknown function but central to the aetiology of Alzheimer s disease. The fact that point and splice mutations lead to an increase in the amount of Ab peptide produced by the cells, provided further support for the amyloid theory about the origin of the disease and, on the other hand, placed these molecules in the central part of this theory. Different groups showed that these proteins had also roles in several cellular pathways, among those, the notch pathway is one of the most important, as it is with the interaction among presenilin 1 and b catenin. Recently, several works have suggested that presenilins are molecules involved in the processing of APP by being an integral part of the protein complex that process the precursor to produce the amyloid peptide. In this paper, I will give an overview of some of the most recent work developed towards the identification of presenilin function and its involvement ...
Nature neuroscience, 1998
Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and relate... more Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and related dementias. Here we review genetic and molecular biological evidence suggesting that the peptide A beta 42 is central to the etiology of AD. Recent data also suggests that dysfunction in the cytoskeletal protein tau is on the pathway that leads to neurodegeneration and dementia. Tau is produced either indirectly, by A beta 42, or directly, in some forms of frontotemporal dementia by mutations in tau itself. These data support are refine the amyloid cascade hypothesis for AD and suggest that understanding the causes and consequences of tau dysfunction is an important priority for dementia research.
Down's syndrome (DS) patients develop the characteristic features of Alzheimer's disease (AD) by ... more Down's syndrome (DS) patients develop the characteristic features of Alzheimer's disease (AD) by their fourth decade, some of them exhibiting an AD-type dementia. We studied the apolipoprotein E (APOE) allele distribution in a population of 41 DS patients comprising 19.5% of demented, compared to 35 control subjects. No statistical difference was observed, but the e2 allele may delay the age of dementia. As described in other studies, the impact of the different APOE alleles in DS is modest. However the compilation of all published studies on AD-type dementia in DS suggests that the e2 allele has a protective effect. In delaying the age of onset, the E2 allele would have a similar action in AD-type dementia in DS and in AD families with amyloid precursor protein (APP) mutations.
Virchows Archiv, 2003
Loss of heterozygosity in the long arm of chromosome 10q is a frequent event in gliomas. It may i... more Loss of heterozygosity in the long arm of chromosome 10q is a frequent event in gliomas. It may involve the LGI1/epitempin gene, which is located in chromosomal region 10q23 approximately 24 and has been proposed to encode a tumor suppressor inactivated in the progression of brain tumors. Nevertheless, so far no data are available demonstrating that the reduced expression of the LGI1 transcript in high-grade astrocytic tumors indeed results in a decreased level of LGI1 protein in the tumor cells. Thus, the aim of the present study was to analyze the expression of the LGI1 protein in a series (ten of each) of pilocytic astrocytomas, astrocytomas [World Health Organization (WHO) grade II], anaplastic astrocytomas (WHO grade III), and glioblastoma multiforme (WHO grade IV). Immunohistochemistry demonstrated a strong expression of the LGI1 protein in normal brain tissue as well as in the majority of pilocytic astrocytomas and astrocytomas (WHO grade II). In anaplastic astrocytomas, the number of tumor cells expressing LGI1 decreased, while LGI1 expression was completely absent from the glioblastomas of this series. This highly significant reduction of LGI1 protein expression in the progression of astrocytic brain tumors lends further support to the hypothesized function of LGI1 as a type-II tumor suppressor gene in glioma pathogenesis.
Trends in Biochemical Sciences, 2002
Recent studies suggest that mutations in the LGI1/Epitempin gene cause autosomal dominant lateral... more Recent studies suggest that mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal epilepsy. This gene encodes a protein of unknown function, which we postulate is secreted. The LGI1 protein has leucine-rich repeats in the N-terminal sequence and a tandem repeat (which we named EPTP) in its C-terminal region. A redefinition of the C-terminal repeat and the application of sensitive sequence analysis methods enabled us to define a new superfamily of proteins carrying varying numbers of the novel EPTP repeats in combination with various extracellular domains. Genes encoding proteins of this family are located in genomic regions associated with epilepsy and other neurological disorders.
Revue Neurologique, 2010
f unit of Molecular genetics, Biomedical institute, valencia, espagne g uSTl, Département des Neu... more f unit of Molecular genetics, Biomedical institute, valencia, espagne g uSTl, Département des Neurosciences, villeneuve d'Ascq, France
Psychiatric Genetics, 2006
A mutation in the FOXP2 gene has been the first genetic association with a language disorder. Lan... more A mutation in the FOXP2 gene has been the first genetic association with a language disorder. Language disorder is considered as a core symptom of schizophrenia. Therefore, the FOXP2 gene could be considered a good candidate gene for the vulnerability to schizophrenia. A set of single nucleotide polymorphisms mainly located in the 5' regulatory region of the FOXP2 gene was analysed in a sample of 186 DSM-IV schizophrenic patients with auditory hallucinations and in 160 healthy controls. Statistically significant differences in the genotype (P=0.007) and allele frequencies (P=0.0027) between schizophrenic patients with auditory hallucinations and controls were found in the single nucleotide polymorphism rs2396753. These P values changed to 0.07 and 0.0273, respectively, after Bonferroni sequential correction. The haplotype rs7803667T/rs10447760C/rs923875A/rs1358278A/rs2396753A (TCAAA) also showed a significant difference confirmed with a permutation test (P=0.009). These results suggested that the FOXP2 gene may confer vulnerability to schizophrenic patients with auditory hallucinations.
Parkinsonism & Related Disorders, 2013
Neuroscience Letters, 1999
In a series of sibpairs with late onset Alzheimer's disease, we have examined the segregation of ... more In a series of sibpairs with late onset Alzheimer's disease, we have examined the segregation of the loci involved in the early onset, autosomal dominant form of the disorder by using¯anking microsatellite repeat markers: thus we have used APP-PCR3 and D21S210 to examine the segregation of the amyloid-b precursor protein (APP) gene, the markers Dl 4S77 and D14S284 to examine the segregation of the presenilin 1 (PSI) gene and the markers D1S227, D1S249 and D1S419 to examine the segregation of presenilin 2 (PS2). We carried out our analyses on the whole dataset of 291 affected sibpairs, and on subsets comprising those sibpairs in which neither had an apolipoprotein E4 allele (65 affected sibpairs) and those in which both had an apolipoprotein E4 allele (165 affected sibpairs). We used the programs SPLINK to generate allele frequencies and MAPMAKER/SIBS to analyze our results. We examined the segregation of the markers D19S908 and D19S918 that are close to the apolipoprotein E (ApoE) gene as a positive control to assess whether the methods we are employing have the capability to identify known loci. The sibpair approach to the identi®cation of genetic risk loci is relatively insensitive as indicated by the failure of the ApoE locus to reach statistical signi®cance (P 0:06). Nevertheless, these data suggest that neither the PS1 nor the PS2 gene is a major locus for late-onset AD, but that the APP gene cannot be ruled out as a risk locus in those sibships without an E4 allele (P 0:014). The possibility that APP is indeed a locus for late onset disease will need con®rmation in other series of familial cases. q
Neuroscience Letters, 1997
Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people. ... more Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people. It usually occurs after 65 years old (late-onset AD). The e4 allele of apolipoprotein E (APOE) gene is a risk factor which contributes about 50% of the genetic risk for this form of the disease. The low density lipoprotein receptor-related protein (LRP) is a major receptor for APOE which is found in the senile plaques of AD brains. This makes it a good candidate gene for the disease. There is a polymorphism in the region upstream of the LRP gene that has been associated with AD in an American population. We examined this polymorphism by restriction fragment length polymorphism analysis in a French population with sporadic late-onset AD. In the previous report, a significant increase of the 87 bp allele was found in the AD cases; however, in our population, we observed a significant decrease with this same allele of the LRP gene. The possible reasons for this discrepancy, linkage disequilibrium or statistical anomaly, are discussed.
Neuroscience Letters, 1999
We have assessed whether apolipoprotein E (ApoE) genotype influences the age of onset of dementia... more We have assessed whether apolipoprotein E (ApoE) genotype influences the age of onset of dementia in a series of families with frontal temporal dementia with defined mutations in the tau gene. In contrast to the situation in Alzheimer's disease (AD), we could find no evidence that the age of onset of disease was influenced by the ApoE genotype.
Neuroscience Letters, 2000
Increasing evidence suggests a relation between vascular disorders and late-onset Alzheimer's dis... more Increasing evidence suggests a relation between vascular disorders and late-onset Alzheimer's disease (AD). We performed an association analysis of low-density lipoprotein receptor-related protein (LRP), lipoprotein lipase (LPL), and angiotensin converting enzyme (ACE) genes, known to be involved in vascular disorders, and AD. Genotyping was carried out in 113 patients with clinically de®ned Alzheimer's disease (NINCDS-ADRDA criteria) and 203 non-demented controls in a prospective, population-based study of people aged 85 years or over (Vantaa 851 Study). Corresponding analysis was performed on 121 neuropathologically veri®ed AD patients (CERAD criteria) and 75 controls derived from the same study population. We did not ®nd signi®cant associations between the polymorphisms studied and AD. However, analysis of the LPL polymorphism showed a weak trend (uncorrected P-value 0.095) towards protection against neuropathologically de®ned AD. Our study is based on very elderly Finns. Therefore, further studies are warranted in other populations. q
Neuroscience Letters, 1999
Using a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (... more Using a combination of polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and DNA sequencing techniques, we identified a unique missence mutation (T → C) in exon 3 of the APOE gene which resulted in the substitution of pro-28 for leu-28. We screened 1118 White cases of late-onset (Ͼ60 years) Alzheimer's disease (AD) from three independent centers (Pittsburgh = 489, Indiana = 319, Mayo Clinic Rochester = 310) and 1123 controls (607 clinically assessed and 516 individuals randomly ascertained from the general population). Two of the 1123 control subjects had the pro-28 mutation (0.18%). However, this mutation was observed in heterozygous state in 2.66, 2.51 and 1.94% of the AD cases from Pittsburgh, Indiana and Mayo Clinic Rochester, respectively, with an overall frequency of 2.42%. All individuals with this mutation were carriers of the APOE*4 allele and hence the mutation was denoted as APOE*4 Pittsburgh (APOE*4P). Compared with the non-E*4P carriers, the E*4P carriers were associated with an increased risk of AD (odds ratio (OR) 13.2) and this risk remained significant even after adjusting for the known effect of APOE*4 (OR 5.4). The risk associated with the E*4P/E*4 combination was about five times (OR 29.1) the risk attributed to APOE*4 carriers alone (OR 5.7). Our data indicates that the new mutation most likely exists in cis-orientation with APOE*4 and is associated with increased risk of developing AD.
Neuroscience Letters, 1999
Recent reports have suggested that variability in the a2-macroglobulin gene is a genetic risk fac... more Recent reports have suggested that variability in the a2-macroglobulin gene is a genetic risk factor for Alzheimer's disease. Here we have both tested a common polymorphism in the gene (I1000V) for association with the disease in a four-site case control study design, and tested the locus for linkage in a large series of sibpairs afflicted with late onset disease. Our results fail to show an association between this polymorphism and disease.
Neuroscience Letters, 1991
A number of polyanions, including polysulfates (sulfated glycosaminoglycans (GAGs), dextran and p... more A number of polyanions, including polysulfates (sulfated glycosaminoglycans (GAGs), dextran and pentosan sulfates, and polyvinylsulfate), polyphosphates (tetrapolyphosphate, polyadenylate) and polycarboxylates (polyaspartate, polyglutamate) solubilize asymmetric acetylcholinesterase (AChE) from chick muscle at low ionic strength, and partially or totally displace AChE tailed forms bound to heparin-agarose columns. The previously reported solubilization of asymmetric AChE by heparin, or the proven affinity of the tailed enzyme forms for this GAG, cannot therefore be taken as direct proof of the involvement of heparin-like heparan sulfate proteoglycans in the anchorage of the collagenous tail of the enzyme to the basal lamina in skeletal muscle.
Neuroscience Letters, 2000
We and others have previously identi®ed two distinct haplotypes of the TAU gene in Caucasian popu... more We and others have previously identi®ed two distinct haplotypes of the TAU gene in Caucasian populations. In this study, we have assessed whether these haplotypes show an association with Alzheimer's disease in a variety of populations. They do not. These data are consistent with the view that the involvement of TAU in Alzheimer's disease is a downstream event. q (J. Hardy).