Biomedical subjects

B Ghetti

Publications and source records attributed to B Ghetti.

At least 55 records · Page 3Linked to original sources

PubMed1999

A cell cycle alteration precedes apoptosis of granule cell precursors in the weaver mouse cerebellum.

A missense mutation in the gene coding for the G-protein-activated inwardly rectifying potassium (GIRK) channel, GIRK2, is responsible for apoptosis in the external germinal layer (EGL) of the cerebellum and a nonapoptotic death of midbrain dopaminergic neurons in the weaver (wv) mouse. Failure of axonogenesis and migration are considered to be the primary consequences of GIRK2 channel malfunction in the cerebellum. We investigated whether a disruption of the cell cycle precedes the failure of migration and axonogenesis and leads to massive apoptosis. To this end, immunohistochemistry and immunoblotting for PCNA, Cdk4, cyclin D, cyclin A, and the Cdk inhibitor p27/kip1, as well as in situ end-labeling for apoptotic DNA fragmentation, were applied to cerebella of P7-P21+/+, wv/+, and wv/wv mice. In +/+ and wv/+ mice, the expression of cell cycle proteins was limited to the outer, premigratory zone of the EGL. Antibodies to p27, a marker of cell differentiation, gave a reverse staining pattern. Due to migration delay, patches of p27-positive cells persisted in the outer EGL in P21 wv/+ mice. On the contrary, marked cell cycle up-regulation and absence of p27 occurred throughout the EGL at all ages in wv/wv mice, indicating an inability to switch off the cell cycle. Mitotic index evaluation showed that cell cycle activation was unrelated to proliferative events. Cell cycle proteins were not expressed in the substantia nigra, suggesting that nonapoptotic death of mature dopaminergic neurons is not preceded by abortive cell cycle re-entry. Our data show that abnormalities of the cell cycle in wv/wv cerebellum represent a major and early consequence of GIRK2 channel malfunction and may strongly influence the susceptibility of EGL cells to apoptosis. These observations may help in understanding the pathogenesis of human neurological channelopathies.

Animals↗

PubMed1999

Tau pathology in a family with dementia and a P301L mutation in tau.

Familial forms of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) have recently been associated with coding region and intronic mutations in the tau gene. Here we report our findings on 2 affected siblings from a family with early-onset dementia, characterized by extensive tau pathology and a Pro to Leu mutation at codon 301 of tau. The proband, a 55-year-old woman, and her 63-year-old brother died after a progressive dementing illness clinically diagnosed as Alzheimer disease. Their mother, 2 sisters, maternal aunt and uncle, and several cousins were also affected. Autopsy in both cases revealed frontotemporal atrophy and degeneration of basal ganglia and substantia nigra. Sequencing of exon 10 of the tau gene revealed a C to T transition at codon 301, resulting in a Pro to Leu substitution. Widespread neuronal and glial inclusions, neuropil threads, and astrocytic plaques similar to those seen in corticobasal degeneration were labeled with a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes spanning the entire tau sequence. Isolated tau filaments had the morphology of narrow twisted ribbons. Sarkosyl-insoluble tau exhibited 2 major bands of 64 and 68 kDa and a minor 72 kDa band, similar to the pattern seen in a familial tauopathy associated with an intronic tau mutation. These pathological tau bands predominantly contained the subset of tau isoforms with 4 microtubule-binding repeats selectively affected by the P301L missense mutation. Our findings emphasize the phenotypic and genetic heterogeneity of tauopathies and highlight intriguing links between FTDP-17 and other neurodegenerative diseases.

Atrophy↗

PubMed1999

Frontotemporal dementia and corticobasal degeneration in a family with a P301S mutation in tau.

The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.

Adult↗

PubMed1999

Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits.

Exonic and intronic mutations in Tau cause familial neurodegenerative syndromes characterized by frontotemporal dementia and dysfunction of multiple cortical and subcortical circuits. Here we describe a G389R mutation in exon 13 of Tau. When 38 years old, the proband presented with progressive aphasia and memory disturbance, followed by apathy, indifference, and hyperphagia. Repeated magnetic resonance imaging showed the dramatic progression of cerebral atrophy. Positron emission tomography revealed marked glucose hypometabolism that was most severe in left frontal, temporal, and parietal cortical regions. Rigidity, pyramidal signs and profound dementia progressed until death at 43 years of age. A paternal uncle, who had died at 43 years of age, had presented with similar symptoms. The proband's brain showed numerous tau-immunoreactive Pick body-like inclusions in the neocortex and the fascia dentata of the hippocampus. In addition, large numbers of tau-positive filamentous inclusions were present in axons in the frontal, temporal, and parietal lobes. Immunoblot analysis of sarkosyl-insoluble tau showed 2 major bands of 60 and 64 kDa. Upon dephosphorylation, these bands resolved into 4 bands consisting of three- and four-repeat tau isoforms. Most isolated tau filaments were straight and resembled filaments found in Alzheimer disease and some frontotemporal dementias with tau mutations. A smaller number of twisted filaments was also observed. Biochemically, recombinant tau proteins with the G389R mutation showed a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. Taken together, the present findings indicate that the G389R mutation in Tau can cause a dementing condition that closely resembles Pick's disease.

Adult↗

PubMed1999

Alteration of IGF system gene expression during the postnatal development of pcd mice.

IGF-I promotes growth during postnatal development via both endocrine and autocrine actions. In pcd mice (pcd/pcd), we previously found that IGF-I mRNA expression was decreased in cerebellar Purkinje cells as they underwent apoptosis. To investigate the endocrine function of IGF-I, we examined hepatic IGF-I mRNA by Northern hybridization, circulating IGF-I peptide by radioimmunoassay, and circulating IGFBP by Western ligand blot in pcd mice. At postnatal days (D) 17 and 24, hepatic IGF-I mRNA and circulating IGF-I and IGF-II concentrations were normal in pcd mice. From D45, both hepatic IGF-I mRNA and circulating IGF-I concentrations decreased. The decrease in circulating IGF-I concentrations was accompanied by a simultaneous increase in circulating IGF-II concentrations in both the D45 and adult pcd mice. An early decrease in the circulating IGFBP-3 levels and an increase in the IGFBP-2 levels were observed at D17 and were followed by decreases in both IGFBPs at D45 and in the adult. Therefore, after the cerebellar neurodegeneration, there was an overall decrease in IGF-I gene expression in pcd mice. Our results suggest that the decrease in IGF-I gene expression may contribute to growth deficiency and multiple system degeneration in pcd mice.

Animals↗

PubMed1999

Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.

Adult↗

PubMed1998

Characterization of murine Girk2 transcript isoforms: structure and differential expression.

A mutation in the G-protein-linked inwardly rectifying K+ channel 2 gene (Girk2) is the cause of the weaver mouse phenotype. We determined that the originally published Girk2 transcript is composed of five exons. The primary coding exon (designated exon 4a in our system) encodes over two-thirds of the protein. Five different full-length Girk2 transcript isoforms (designated Girk2-1, Girk2A-1, Girk2A-2, Girk2B, and Girk2C) originating from different transcriptional start sites and/or alternative splicing were isolated by cDNA RACE. Several of the transcripts were predicted to encode truncated proteins that may lack some of the G-proteincoupling sequence. Northern blotting and in situ hybridization studies with transcript-specific probes indicated that the transcripts were differentially expressed in both normal and weaver mice. All transcripts tested were expressed in the three major targets of action of the weaver mutation: cerebellum, substantia nigra, and testis. Two of the transcripts, Girk2A-1 and Girk2A-2, encode identical proteins and have a distinct pattern of expression in testis, which suggests that they are associated with specific stages of spermatogenesis. An additional transcript, Girk2D, appears to be brain-specific, not polyadenylated, and highly expressed in cerebellar granule cells.

Animals↗

PubMed1998

Mutation in the tau gene in familial multiple system tauopathy with presenile dementia.

Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3' neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer's disease and other tauopathies.

Adenine↗

PubMed1998

Altered responses to potassium in cerebellar neurons from weaver heterozygote mice.

The pleiotropic weaver disease is caused by the mutation of a single amino acid in the G-protein-linked inwardly rectifying K+ channel, GIRK2. In homozygous (wv/wv) animals, the disease is characterized by loss of cerebellar and dopaminergic mesencephalic neurons as well as testicular cells, which produce ataxia, fine tremors, and sterility, respectively. Heterozygous (wv/+) animals show no obvious motor impairments, although some loss of both cerebellar and dopaminergic neurons is observed and wv/+ males become sterile at 3.5 months of age. Abnormal influxes of Na+ and Ca2+ have been linked to cerebellar cell death in wv/wv animals, but it's not clear whether similar changes are observed in wv/+ animals. To discover whether changes in K+-channel function or intracellular Ca2+ concentrations ([Ca2+]i) play a role in the augmented cell loss observed in wv/+ animals when compared with +/+ animals, we studied cultured cerebellar granule cells prepared from either wv/+ or +/+ animals. Resting [Ca2+]i was elevated in wv/+ relative to +/+ animals. Further, depolarizations of cells with elevated K+ solutions elicited much smaller changes in [Ca2+]i in wv/+ animals than in +/+ animals, presumably due to altered GIRK2 channel function. Both wv/+ and +/+ cells showed similar changes in [Ca2+]i when cells were depolarized by glutamate (1 mM), suggesting that both glutamate receptors and Ca2+ channels were unchanged in wv/ + animals. In summary, our results suggest that wv/+ cerebellar granule cells exhibit elevated resting [Ca2+]i levels and altered K+-channel function, which may contribute to the developmental abnormalities and increased cell death observed.

Animals↗

PubMed1998

Lewy bodies contain altered alpha-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes.

Missense mutations in the alpha-synuclein gene cause familial Parkinson's disease (PD), and alpha-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether alpha-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n = 65) or amyloid precursor protein (n = 9) genes, studies were conducted with antibodies to alpha-, beta-, and gamma-synuclein. LBs were detected with alpha- but not beta- or gamma-synuclein antibodies in 22% of FAD brains, and alpha-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained alpha-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, alpha-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of alpha-synuclein was reduced compared with control brains. The presence of alpha-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble alpha-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain.

Adult↗

PubMed1998

Endogenous proteolytic cleavage of normal and disease-associated isoforms of the human prion protein in neural and non-neural tissues.

We have investigated the proteolytic cleavage of the cellular (PrPC) and pathological (PrPSc) isoforms of the human prion protein (PrP) in normal and prion-affected brains and in tonsils and platelets from neurologically intact individuals. The various PrP species were resolved after deglycosylation according to their electrophoretic mobility, immunoreactivity, Sarkosyl solubility, and, as a novel approach, resistance to endogenous proteases. First, our data show that PrPC proteolysis in brain originates amino-truncated peptides of 21 to 22 and 18 (C1) kd that are similar in different regions and are not modified by the PrP codon 129 genotype, a polymorphism that affects the expression of prion disorders. Second, this proteolytic cleavage of PrPC in brain is blocked by inhibitors of metalloproteases. Third, differences in PrPC proteolysis, and probably in Asn glycosylation and glycosylphosphatidylinositol anchor composition, exist between neural and non-neural tissues. Fourth, protease-resistant PrPSc cores in sporadic Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker F198S disease brains all have an intact C1 cleavage site (Met111-His112), which precludes disruption of a domain associated with toxicity and fibrillogenesis. Fifth, the profile of endogenous proteolytic PrPSc peptides is characteristic of each disorder studied, thus permitting the molecular classification of these prion diseases without the use of proteinase K and even a recognition of PrPSc heterogeneity within type 2 CJD patients having different codon 129 genotype and neuropathological phenotype. This does not exclude the role of additional factors in phenotypic expression; in particular, differences in glycosylation that may be especially relevant in the new variant CJD. Proteolytic processing of PrP may play an important role in the neurotropism and phenotypic expression of prion diseases, but it does not appear to participate in disease susceptibility.

Aged↗

PubMed1998

Neurological illness in transgenic mice expressing a prion protein with an insertional mutation.

Familial prion diseases are caused by mutations in the gene encoding the prion protein (PrP). We have produced transgenic mice that express the mouse homolog of a mutant human PrP containing a nine octapeptide insertion associated with prion dementia. These mice exhibit a slowly progressive neurological disorder characterized clinically by ataxia and neuropathologically by cerebellar atrophy and granule cell loss, gliosis, and PrP deposition that is most prominent in the cerebellum and hippocampus. Mutant PrP molecules expressed in the brains of these mice are resistant to digestion by low concentrations of proteinase K and display several other biochemical properties reminiscent of PrP(Sc), the pathogenic isoform of PrP. These results establish a new transgenic animal model of an inherited human prion disorder.

Animals↗

PubMed1998

Phenotypic variability of Gerstmann-Sträussler-Scheinker disease is associated with prion protein heterogeneity.

Gerstmann-Sträussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt-Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.

Adult↗

PubMed1998

FDG-PET and MRI in temporal lobe epilepsy: relationship to febrile seizures, hippocampal sclerosis and outcome.

OBJECTIVE: To correlate the volumetric head magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan findings with the history, intracarotid amobarbital procedure, pathology, and outcome in patients with medically refractory temporal lobe epilepsy. MATERIAL AND METHODS: Thirty-eight patients with temporal lobe epilepsy treated surgically following a comprehensive presurgical evaluation. Follow-up ranged from 12 to 44 months. RESULTS: Volumetric MRI showed ipsilateral hippocampal atrophy in 29 (76%), and PET scan showed ipsilateral temporal hypometabolism (PET-TH) in 31 (81.5%) of patients. Eighty-three percent of those patients with hippocampal sclerosis on MRI (MRI-HS) had ipsilateral PET-TH. Sixty-six percent of patients with MRI-HS had a history of prolonged febrile convulsions or a childhood febrile illness accompanied by convulsions, and 77% of patients with MRI-HS had pathologically proven hippocampal sclerosis (HS). Ninety percent became seizure free or had rare seizures. CONCLUSION: FDG-PET scans and head MRIs were complementary; 95% of patients had either MRI-HS or temporal hypometabolism. MRI-HS correlated with a history of febrile seizures and pathologically demonstrated hippocampal sclerosis. Ninety-three percent of patients had focal functional deficits on the epileptogenic side. Concordance between PET temporal hypometabolism and MRI-HS correlated with better outcome.

Adolescent↗

PubMed1998

Frontotemporal dementia and Parkinsonism linked to chromosome 17: a new group of tauopathies.

Frontotemporal dementia is a neurological disorder characterised by personality changes, deterioration of memory and executive functions as well as stereotypical behaviour. Sometimes a Parkinsonian syndrome is prominent. Several cases of frontotemporal dementia are hereditary and recently families have been identified where the disease is linked to chromosome 17q21-22. Although, there is clinical and neuropathological variability among and within families, they all consistently present a symptomathology that has led investigators to name the disease "Frontotemporal Dementia and Parkinsonism linked to chromosome 17." Neuropathologically, these patients present with atrophy of frontal and temporal cortex as well as of basal ganglia and substantia nigra. In the majority of cases these features are accompanied by neuronal loss, gliosis and microtubule-associated protein tau deposits which can be present in both neurones and glial cells. The distribution, structural and biochemical characteristics of the tau deposits differentiate them from those present in Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy and Pick's disease. No beta-amyloid deposits are present. The clinical and neuropathological features of the disease in these families suggest that Frontotemporal Dementia and Parkinsonism linked to chromosome 17 is a distinct disorder. The presence of abundant tau deposits in the majority of these families define this disorder as a new tauopathy.

Brain↗

PubMed1998

Hypothalamic-pituitary-gonadal axis in the mutant weaver mouse.

The weaver (wv) mutant mouse manifests severe locomotor defects, a deficiency in granule cells of the cerebellum, and cellular deficits in the midbrain dopaminergic system. The wv phenotype is associated with a missense mutation in the pore region of the G-protein-gated inwardly rectifying potassium channel, GIRK2. The homozygous male wv mouse is essentially infertile due to an inadequate level of sperm production. Females are fertile although they also manifest the neurological phenotype. Homozygotes of both sexes have reduced body weight. We have evaluated the hypothalamic-pituitary-gonadal axis in heterozygote and homozygote male and female wv mutants in comparison with wild-type controls. Testicular weight was significantly reduced in the homozygous males, due to degenerative changes of seminiferous epithelium. Serum and pituitary content of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were normal in all groups, and the normal sex differences were noted (FSH and LH higher in males, prolactin higher in females). Pituitary growth hormone (GH) concentration was normal, with control and mutant males showing higher GH than females. Serum testosterone levels were normal in the mutants, as was testicular testosterone. Testicular alpha-inhibin content was mildly reduced, but high in proportion to testicular weight. The defect in spermatogenesis appeared predominantly in the postmeiotic stages. In situ hybridization was consistent with expression of some GIRK2 mRNA isoforms in seminiferous epithelium. There were no significant differences between genotypes in the levels of dopamine, dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the mediobasal and preoptic hypothalamic regions. Homovanillic acid levels in these two areas were, however, reduced in wv homozygotes compared to wild-type animals. In the light of normal pituitary hormone levels, normal hypothalamic monoamine concentrations and normal sex differences in gonadotropins, we conclude that the infertility in the male homozygote wv mouse lies within the tubule and is probably a primary defect in the germ cells. The hormonal data suggest that Leydig cell function, and at least some aspects of Sertoli cell function, are normal in the mutant mice.

Animals↗

PubMed1998

Creutzfeldt-Jakob disease in a husband and wife.

A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife.

Animals↗

PubMed1998

An antibody raised against a conserved sequence of the prion protein recognizes pathological isoforms in human and animal prion diseases, including Creutzfeldt-Jakob disease and bovine spongiform encephalopathy.

Antibodies to the prion protein (PrP) have been critical to the neuropathological and biochemical characterization of PrP-related degenerative diseases in humans and animals. Although PrP is highly conserved evolutionarily, there is some sequence divergence among species; as a consequence, anti-PrP antibodies have a wide spectrum of reactivity (from strong immunopositivity to lack of reactivity) when challenged with PrP from diverse species. We have produced an antibody (anti-PrP95-108) raised against a synthetic peptide corresponding to residues 95 to 108 of human PrP and have characterized it by epitope mapping, Western immunoblot analysis, and immunohistochemistry. The antibody recognizes not only human PrP isoforms but also pathological PrP from all species tested (ie, cattle, sheep, hamsters, and mice). This is probably due to the fact that the epitope recognized by this antibody includes residues 100 to 108 of human PrP, a sequence that is also present in PrP of several other species. Thus, this reagent is valuable not only for the study of human prion diseases but also for analysis of the possible relationship between human and animal disorders.

Amino Acid Sequence↗