• Gerstmann-Sträussler-Scheinker syndrome
• Neurodegenerative diseases
• Next generation sequencing
• PRNP gene

• Animals
• Humans
• Gerstmann-Straussler-Scheinker Disease/diagnosis
• Gerstmann-Straussler-Scheinker Disease/genetics
• Gerstmann-Straussler-Scheinker Disease/metabolism
• Prions/genetics
• Prion Proteins/genetics
• Mutation/genetics
• High-Throughput Nucleotide Sequencing

• (RC 2773804) Ministero della Salute

• Creutzfeldt–Jakob disease
• MRI-diffusion-weighted image
• chronic wasting disease
• diagnostic criteria
• prion
• protein misfolding cyclic amplification
• real-time quaking-induced conversion

• Humans
• Creutzfeldt-Jakob Syndrome/diagnosis
• Prion Diseases/diagnosis
• Early Diagnosis
• Encephalitis
• Phenotype

• CJD, Creutzfeldt-Jakob disease
• Codon 129
• Codon 219
• Creutzfeldt-jakob disease
• Dimer
• E, glutamate
• Electrostatic interaction
• GSS, Gerstmann-Straussler-Scheinker disease
• Genetic prion disease
• Heterozygosity
• K, lysine
• M, methionine
• OR, odds ratio
• PRNP
• Polymorphism
• PrP, prion protein
• Prion
• V, valine

Gerstmann–Sträussler–Scheinker disease (GSS) is a rare neurodegenerative illness that belongs to the group of hereditary or familial Transmissible Spongiform Encephalopathies (TSE). Due to the presence of different pathogenic alterations in the prion protein (PrP) coding gene, it shows an enhanced proneness to misfolding into its pathogenic isoform, leading to prion formation and propagation. This aberrantly folded protein is able to induce its conformation to the native counterparts forming amyloid fibrils and plaques partially resistant to protease degradation and showing neurotoxic properties. PrP with A117V pathogenic variant is the second most common genetic alteration leading to GSS and despite common phenotypic and neuropathological traits can be defined for each specific variant, strikingly heterogeneous manifestations have been reported for inter-familial cases bearing the same pathogenic variant or even within the same family. Given the scarcity of cases and their clinical, neuropathological, and biochemical variability, it is important to characterize thoroughly each reported case to establish potential correlations between clinical, neuropathological and biochemical hallmarks that could help to define disease subtypes. With that purpose in mind, this manuscript aims to provide a detailed report of the first Spanish GSS case associated with A117V variant including clinical, genetic, neuropathological and biochemical data, which could help define in the future potential disease subtypes and thus, explain the high heterogeneity observed in patients suffering from these maladies.

• Gerstmann–Sträussler–Scheinker disease
• Inherited prion disease
• Neurodegeneration
• Neuropathology
• Prion disease
• Transmissible spongiform encephalopathy

• Amyloid/genetics
• Gerstmann-Straussler-Scheinker Disease/genetics
• Gerstmann-Straussler-Scheinker Disease/metabolism
• Gerstmann-Straussler-Scheinker Disease/pathology
• Humans
• Mutation
• Plaque, Amyloid
• Prions/genetics
• Prions/metabolism

• Ministerio de Ciencia, Innovación y Universidades
• Interreg

Gerstmann-Sträussler-Scheinker disease (GSS) with a proline-to-leucine mutation at codon 102 (P102L) in the PRNP gene is the most frequently reported GSS subtype worldwide. This study aimed to determine the epidemiological, clinical, genetic, and laboratory characteristics of 12 Chinese patients with P102L-associated GSS (henceforth P102L GSS).

The enrolled P102L GSS cases were analyzed according to the diagnostic criteria for Creutzfeldt-Jakob disease (CJD) issued by the China National Health Commission.

The median onset age was 50 years (range 34 to 67 years) and sex ratio was 1:2 (males:females). Most patients displayed more than one foremost symptom. Movement symptoms were frequently reported (9 of the 12 cases), followed by rapidly progressing dementia (7 cases), mental problems (5 cases), and slowly progressing dementia (2 cases). Almost all cases displayed more sporadic CJD (sCJD)-associated neurological symptoms and signs as time progressed. Five (45.5%) of 11 cases were cerebrospinal fluid 14-3-3 positive, and 2 (25%) of 8 cases exhibited periodic sharp wave complexes in electroencephalograms. MRI abnormalities were detected in all 11 of the scanned patients. Methionine homozygous genotype at codon 129 (M129M) and glutamic acid homozygous at codon 219 (E219E) homozygosity was present in 11 cases, while 1 case was M129M homozygous and glutamic acid/lysine heterozygous at codon 219 (E219K) heterozygous. Ten of the 12 cases recalled a disease-related family history during the clinical interviews. The median survival from symptom onset of the seven dead cases was 16 months (range 10 to 44 months). Patients showing the sCJD phenotype (rapidly progressing dementia) appeared to be associated with a shorter survival time.

The indistinguishable clinical features of P102L GSS patients with sCJD, especially in the early stage, support the importance of PRNP testing for diagnosing GSS.

• Gerstmann-Sträussler-Scheinker disease
• PRNP
• prions
• proline-to-leucine mutation at codon 102 mutation

Gerstmann-Sträussler-Scheinker (GSS) disease is an inherited prion disease that is clinically characterized by the early onset of progressive cerebellar ataxia. The incidence of GSS is extremely low and it is particularly rare in China. Therefore, clinicians may easily confuse this disease with other diseases that also cause ataxia, resulting in its under-diagnosis or misdiagnosis.

Here, we report the first case of genetically diagnosed GSS disease in Northeast China. The patient exhibited typical ataxia and dysarthria 2.5 years after symptom onset. However, magnetic resonance imaging of the brain and spinal cord revealed a normal anatomy. Screening results for the spinocerebellar ataxia gene were also negative. We thus proposed to expand the scope of genetic screening to include over 200 mutations that can cause ataxia. A final diagnosis of GSS was presented and the patient was followed for more than 3.5 years, during which we noted imaging abnormalities. The patient gradually exhibited decorticate posturing and convulsions. We recommended administration of oral sodium valproate, which resolved the convulsions.

Patients with inherited ataxia should be considered for a diagnosis of GSS via genetic testing at an early disease stage.

• Prion disease
• Cerebellar ataxia
• Magnetic resonance imaging
• Diagnosis
• Brain
• Case report

• Creutzfeld-Jakob disease
• Parkinsonism
• prion

Inherited prion diseases (IPDs), including genetic Creutzfeldt-Jakob disease (gCJD), account for 10–15% of cases of prion diseases and are associated with several pathogenic mutations, including P102L, V180I, and E200K, in the prion protein gene (PRNP). The valine to isoleucine substitution at codon 180 (V180I) of PRNP is the most common pathogenic mutation causing gCJD in East Asian patients. In this study, we conducted follow-up analyses to identify candidate factors and their associations with disease onset. Whole-genome sequencing (WGS) data of five gCJD patients with V180I mutation and 145 healthy individuals were used to identify genomic differences. A total of 18,648,850 candidate variants were observed in only the patient group, 29 of them were validated as variants. Four of these validated variants were nonsense mutations, six were observed in genes directly or indirectly related to neurodegenerative disorders (NDs), such as LPA, LRRK2, and FGF20. More than half of validated variants were categorized in Gene Ontology (GO) terms of binding and/or catalytic activity. Moreover, we found differential genome variants in gCJD patients with V180I mutation, including one uniquely surviving 10 years after diagnosis of the disease. Elucidation of the relationships between gCJD and Alzheimer’s disease or Parkinson’s disease at the genomic level will facilitate further advances in our understanding of the specific mechanisms mediating the pathogenesis of NDs and gold standard therapies for NDs.

• Aged
• Amino Acid Substitution
• Codon
• Computational Biology
• Creutzfeldt-Jakob Syndrome/diagnosis
• Creutzfeldt-Jakob Syndrome/genetics
• Creutzfeldt-Jakob Syndrome/metabolism
• Disease Progression
• Epistasis, Genetic
• Female
• Gene Ontology
• Gene Regulatory Networks
• Genomics/methods
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Middle Aged
• Mutation
• Neurodegenerative Diseases/genetics
• Neurodegenerative Diseases/metabolism
• Phenotype
• Prion Proteins/genetics
• tau Proteins/metabolism

• Ministry of Health and Welfare

Gerstmann-Sträussler-Scheinker disease (GSS) is an inherited neurodegenerative disorder associated with mutations in the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrP^res) of 6–8 kDa. With the exception of a few GSS cases characterized by co-accumulation of PrP^res of 21 kDa, efforts to transmit GSS to rodents have been unsuccessful. As a result, GSS subtypes exclusively associated with 6–8 kDa PrP^res have often been considered as non-transmissible proteinopathies rather than true prion diseases. We show that GSS with P102L, A117V and F198S mutations transmit efficiently and produce distinct pathological phenotypes in bank voles (M. glareolus), irrespective of the presence of 21 kDa PrP^res in the inoculum, demonstrating that GSS is a genuine prion disease characterized by both transmissibility and strain variation.

The A117V mutation enhances the aggregation propensity of the palindromic sequences in prion protein.

• prion
• cellular prion protein
• prp^c
• misfolded prion protein
• prp^sc
• prnp
• amyloid
• α-helices
• β-sheets

• Amyloid/chemistry
• Animals
• Humans
• Models, Structural
• PrPC Proteins/chemistry
• PrPSc Proteins/chemistry
• Prion Proteins/chemistry
• Prion Proteins/genetics
• Prions/chemistry
• Prions/physiology
• Protein Folding

Human prion diseases are caused by abnormal accumulation of misfolded prion protein in the brain tissue. Inherited prion diseases, including familial Creutzfeldt-Jakob disease (fCJD), are associated with mutations of the prion protein gene (PRNP). The glutamate (E)-to-lysine (K) substitution at codon 200 (E200K) in PRNP is the most common pathogenic mutation causing fCJD, but the E200K pathogenic mutation alone is regarded insufficient to cause prion diseases; thus, additional unidentified factors are proposed to explain the penetrance of E200K-dependent fCJD. Here, exome differences and biological network analysis between fCJD patients with E200K and healthy individuals, including a non-CJD individual with E200K, were analysed to gain new insights into possible mechanisms for CJD in individuals carrying E200K.

Exome sequencing of the three CJD patients with E200K and 11 of the family of one patient (case1) were performed using the Illumina HiSeq 2000. The exome sequences of 24 Healthy Koreans were used as control. The bioinformatic analysis of the exome sequences was performed using the CLC Genomics Workbench v5.5. Sanger sequencing for variants validation was processed using a BigDye Terminator Cycle Sequencing Kit and an ABI 3730xl automated sequencer. Biological networks were created using Cytoscape (v2.8.3 and v3.0.2) and Pathway Studio 9.0 software.

Nineteen sites were only observed in healthy individuals. Four proteins (NRXN2, KLKB1, KARS, and LAMA3) that harbour rarely observed single-nucleotide variants showed biological interactions that are associated with prion diseases and/or prion protein in our biological network analysis.

Through this study, we confirmed that individuals can have a CJD-free life, even if they carry a pathogenic E200K mutation. Our research provides a possible mechanism that involves a candidate protective factor; this could be exploited to prevent fCJD onset in individuals carrying E200K.

• Creutzfeldt-Jakob Disease
• Genome-Wide Association Study
• Mutation
• Polymorphism, Single Nucleotide
• Prion Diseases
• Prion Protein Gene

• Europe
• Asia, Eastern
• Humans
• Mutation
• Polymorphism, Single Nucleotide
• Prion Diseases/epidemiology
• Prion Diseases/genetics
• Prion Proteins
• Prions/genetics

• Amino Acid Sequence
• Amyloid/chemistry
• Computer Simulation
• Humans
• Hydrogen Bonding
• Hydrophobic and Hydrophilic Interactions
• Models, Molecular
• Molecular Sequence Data
• Monte Carlo Method
• Mutation
• Peptides/chemistry
• Peptides/genetics
• PrPC Proteins/chemistry
• PrPC Proteins/genetics
• Prions/chemistry
• Prions/genetics
• Protein Conformation
• Protein Multimerization
• Protein Structure, Secondary
• Thermodynamics

• BBS/E/D/20251967 Biotechnology and Biological Sciences Research Council
• BBS/E/D/20251968 Biotechnology and Biological Sciences Research Council
• BB/J004332/1 Biotechnology and Biological Sciences Research Council

• Electrophysiology
• Membrane Proteins
• Potassium Channels
• Prions
• Protein Cross-linking

While prions play a central role in the pathogenesis of transmissible spongiform encephalopathies, the biology of these proteins and the pathophysiology of these diseases remain largely unknown. Since no case of bovine spongiform encephalopathy (BSE) has ever been reported in buffalo despite their phylogenetic proximity to cattle, genetic differences may be driving the different susceptibilities of these two species to BSE. We thus hypothesized that differences in expression of the most recently identified member of the prion family or Shadoo (SPRN) gene may relate to these species-specific differences.

We first analyzed and compared the polymorphisms of the SPRN gene (∼4.4 kb), including the putative promoter, coding and 3′ regions, and further verified the entire ORF and putative promoter. This yielded a total of 117 fixed differences, remarkably: 1) a 12-bp insertion/deletion polymorphism in the hydrophobic domain of the cattle but not buffalo gene, introducing a four amino acid expansion/contraction in a series of 5 tandem Ala/Gly-containing repeats; 2) two fixed missense mutations (102Ser→Gly and 119Thr→Ala), and three missense mutations (92Pro>Thr/Met, 122Thr>Ile and 139Arg>Trp) in the coding region presenting different (P<0.05) genotypic and allelic frequency distributions between cattle and buffalo; and, 3) functional luciferase-reporter experiments for the predicted promoter region, consistent with a significantly higher activity in buffalo than cattle. Supporting these findings, immunoblotting revealed higher relative expression levels of Sho protein in cerebrum from buffalo than from cattle. In addition, for cattle, highest Sho expression was detected in obex, as compared to cerebrum or cerebellum.

Our findings support Sho as a non-PrP specific marker for prion infections, with obex as the best tissue source for the detection of Sho in TSE rapid tests. Moreover, these discoveries may prove advantageous for further understanding the biology of prion diseases.

• Amino Acid Sequence
• Animals
• Base Sequence
• Binding Sites
• Brain/metabolism
• Buffaloes/genetics
• Cattle/genetics
• Encephalopathy, Bovine Spongiform/genetics
• Gene Components
• Gene Expression
• Gene Frequency
• Genes, Reporter
• INDEL Mutation
• Luciferases, Renilla/biosynthesis
• Luciferases, Renilla/genetics
• Mutation, Missense
• Nerve Tissue Proteins/genetics
• Nerve Tissue Proteins/metabolism
• Organ Specificity
• Polymorphism, Genetic
• Protein Structure, Tertiary
• Repetitive Sequences, Nucleic Acid
• Sequence Analysis, DNA
• Sequence Homology, Nucleic Acid

• Animals
• Cattle
• Creutzfeldt-Jakob Syndrome/epidemiology
• Creutzfeldt-Jakob Syndrome/genetics
• Creutzfeldt-Jakob Syndrome/metabolism
• Creutzfeldt-Jakob Syndrome/pathology
• Humans
• Kuru/epidemiology
• Kuru/genetics
• Kuru/metabolism
• Kuru/pathology
• Mutation
• PrPSc Proteins/genetics
• PrPSc Proteins/metabolism
• Protein Folding

• Animals
• Cell Line, Transformed
• Enzyme Inhibitors/pharmacology
• Gene Expression/physiology
• Gene Expression Profiling/methods
• Hypothalamus/cytology
• Infections
• Mice
• Neurons/drug effects
• Neurons/metabolism
• Oligonucleotide Array Sequence Analysis/methods
• Prions/metabolism
• Quinacrine/pharmacology

• GGP04147 Telethon
• Cancer Research UK

• Adult
• Asian People
• Brain/pathology
• Female
• Gerstmann-Straussler-Scheinker Disease/genetics
• Gerstmann-Straussler-Scheinker Disease/pathology
• Humans
• Immunohistochemistry
• Magnetic Resonance Imaging
• Male
• Microscopy, Electron, Transmission
• Pedigree
• Point Mutation
• Prions/genetics

• Adult
• Aged
• Aged, 80 and over
• Alleles
• Case-Control Studies
• Codon/genetics
• Creutzfeldt-Jakob Syndrome/genetics
• Female
• Genotype
• Haplotypes
• Homozygote
• Humans
• Male
• Microsatellite Repeats
• Middle Aged
• Phenotype
• Polymorphism, Genetic
• Prion Proteins
• Prions/genetics

Trait heterogeneity, which exists when a trait has been defined with insufficient specificity such that it is actually two or more distinct traits, has been implicated as a confounding factor in traditional statistical genetics of complex human disease. In the absence of detailed phenotypic data collected consistently in combination with genetic data, unsupervised computational methodologies offer the potential for discovering underlying trait heterogeneity. The performance of three such methods – Bayesian Classification, Hypergraph-Based Clustering, and Fuzzy k-Modes Clustering – appropriate for categorical data were compared. Also tested was the ability of these methods to detect trait heterogeneity in the presence of locus heterogeneity and/or gene-gene interaction, which are two other complicating factors in discovering genetic models of complex human disease. To determine the efficacy of applying the Bayesian Classification method to real data, the reliability of its internal clustering metrics at finding good clusterings was evaluated using permutation testing.

Bayesian Classification outperformed the other two methods, with the exception that the Fuzzy k-Modes Clustering performed best on the most complex genetic model. Bayesian Classification achieved excellent recovery for 75% of the datasets simulated under the simplest genetic model, while it achieved moderate recovery for 56% of datasets with a sample size of 500 or more (across all simulated models) and for 86% of datasets with 10 or fewer nonfunctional loci (across all simulated models). Neither Hypergraph Clustering nor Fuzzy k-Modes Clustering achieved good or excellent cluster recovery for a majority of datasets even under a restricted set of conditions. When using the average log of class strength as the internal clustering metric, the false positive rate was controlled very well, at three percent or less for all three significance levels (0.01, 0.05, 0.10), and the false negative rate was acceptably low (18 percent) for the least stringent significance level of 0.10.

Bayesian Classification shows promise as an unsupervised computational method for dissecting trait heterogeneity in genotypic data. Its control of false positive and false negative rates lends confidence to the validity of its results. Further investigation of how different parameter settings may improve the performance of Bayesian Classification, especially under more complex genetic models, is ongoing.

• Algorithms
• Bayes Theorem
• Cluster Analysis
• Computer Simulation
• Fuzzy Logic
• Genetic Heterogeneity
• Genetic Predisposition to Disease
• Genotype
• Models, Genetic
• Phenotype
• Quantitative Trait Loci

• R01 HL065234 NHLBI NIH HHS
• HL65234 NHLBI NIH HHS
• U19 HL065962 NHLBI NIH HHS
• P20 RR018787 NCRR NIH HHS
• U01 HL065962 NHLBI NIH HHS
• RR018787 NCRR NIH HHS
• R01 AI059694 NIAID NIH HHS
• R01 HD047447 NICHD NIH HHS
• T32 MH064913 NIMH NIH HHS
• AI59694 NIAID NIH HHS
• T32 MH64913 NIMH NIH HHS
• N532830 PHS HHS
• HD047447 NICHD NIH HHS
• A619085 PHS HHS

• Aged
• Amino Acid Sequence
• Apolipoproteins E/genetics
• Base Sequence
• Creutzfeldt-Jakob Syndrome/genetics
• Female
• GPI-Linked Proteins
• Gene Frequency
• Genetic Predisposition to Disease
• Humans
• Korea
• Linkage Disequilibrium/genetics
• Male
• Middle Aged
• Open Reading Frames
• Polymorphism, Single Nucleotide
• Prions/genetics
• Untranslated Regions

• Genetic Diseases, Inborn/genetics
• Genetic Heterogeneity
• Genetics, Medical/methods
• Genetics, Medical/trends
• Humans
• Models, Genetic
• Models, Statistical
• Phenotype
• Polymorphism, Single Nucleotide
• Quantitative Trait Loci

• A619085 PHS HHS
• AI 59694 NIAID NIH HHS
• HL 65234 NHLBI NIH HHS
• NS 32830 NINDS NIH HHS
• T32 MH 64913 NIMH NIH HHS

• Alleles
• Chromatography, High Pressure Liquid/methods
• Genetic Variation/genetics
• Humans
• Prions/analysis
• Prions/genetics
• Protein Denaturation

• Alleles
• Amino Acid Sequence
• Base Sequence
• Codon
• Gene Frequency
• Genotype
• Glutamic Acid/chemistry
• Heterozygote
• Homozygote
• Humans
• Korea
• Lysine/chemistry
• Methionine/chemistry
• Molecular Sequence Data
• Open Reading Frames
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Polymorphism, Restriction Fragment Length
• Prions/genetics
• Valine/chemistry

• Amyloid/chemistry
• Amyloid/metabolism
• Amyloid/ultrastructure
• Dimerization
• Guanidine
• Humans
• Hydrogen-Ion Concentration
• Mutagenesis, Site-Directed
• Mutation, Missense
• Proline
• Protein Denaturation
• beta 2-Microglobulin/chemistry
• beta 2-Microglobulin/ultrastructure

• Adult
• Chromosomes, Human, Pair 20
• Codon
• DNA Mutational Analysis
• Depression/etiology
• Depression/genetics
• Genotype
• Gerstmann-Straussler-Scheinker Disease/complications
• Gerstmann-Straussler-Scheinker Disease/genetics
• Gerstmann-Straussler-Scheinker Disease/psychology
• Humans
• Male
• Mood Disorders/genetics
• Phenotype
• Point Mutation
• Polymorphism, Genetic
• Prions/genetics

• Carbohydrate Sequence
• Chromatography, High Pressure Liquid
• Chromatography, Ion Exchange
• Electrophoresis, Gel, Two-Dimensional
• Electrophoresis, Polyacrylamide Gel
• Glycolipids/chemistry
• Glycosylphosphatidylinositols
• Lectins/metabolism
• Mannosidases/chemistry
• Mass Spectrometry/methods
• Molecular Sequence Data
• N-Acetylneuraminic Acid
• Phosphatidylinositols/chemistry
• PrPSc Proteins
• Prions/chemistry
• Prions/isolation & purification
• Sialic Acids/analysis
• alpha-Mannosidase

• AG02132 NIA NIH HHS
• NS14069 NINDS NIH HHS
• NS22786 NINDS NIH HHS

• Amyloid beta-Peptides/metabolism
• Astrocytes/metabolism
• Astrocytes/ultrastructure
• Brain/metabolism
• Brain/pathology
• Brain/ultrastructure
• Family Health
• Female
• Gerstmann-Straussler-Scheinker Disease/complications
• Gerstmann-Straussler-Scheinker Disease/genetics
• Gerstmann-Straussler-Scheinker Disease/metabolism
• Gerstmann-Straussler-Scheinker Disease/pathology
• Glial Fibrillary Acidic Protein/metabolism
• Humans
• Immunohistochemistry
• Inclusion Bodies/pathology
• Inclusion Bodies/ultrastructure
• Leucine/genetics
• Microscopy, Electron
• Middle Aged
• Mutation
• Organ Size
• Pedigree
• Prions/genetics
• Prions/metabolism
• Proline/genetics
• S100 Proteins/metabolism
• Schizophrenia/complications
• Schizophrenia/genetics
• Schizophrenia/pathology
• Staining and Labeling/methods
• Ubiquitin/metabolism

• Animals
• Brain/metabolism
• Cattle
• Creutzfeldt-Jakob Syndrome/transmission
• Deer
• Encephalopathy, Bovine Spongiform/transmission
• Humans
• Mice
• Mice, Transgenic
• Mink
• Models, Animal
• PrPSc Proteins/metabolism
• Prion Diseases/etiology
• Prion Diseases/transmission
• Prion Diseases/virology
• Prions/genetics
• Scrapie/transmission
• Sheep
• Wasting Disease, Chronic/etiology

• Alzheimer Disease/classification
• Alzheimer Disease/diagnosis
• Alzheimer Disease/genetics
• Cerebral Amyloid Angiopathy/classification
• Cerebral Amyloid Angiopathy/diagnosis
• Cerebral Amyloid Angiopathy/genetics
• DNA Mutational Analysis
• Dementia/classification
• Dementia/diagnosis
• Dementia/genetics
• Dementia, Multi-Infarct/classification
• Dementia, Multi-Infarct/diagnosis
• Dementia, Multi-Infarct/genetics
• Genetic Markers/genetics
• Genetic Testing
• Molecular Diagnostic Techniques
• Prion Diseases/classification
• Prion Diseases/diagnosis
• Prion Diseases/genetics

• P50 AG008671 NIA NIH HHS
• P50 AG08671 NIA NIH HHS

• Brain Diseases/genetics
• Dementia/genetics
• Family Health
• Humans
• Mutation
• Neuropeptides/genetics
• Protein Conformation
• Serpins/chemistry
• Serpins/genetics
• alpha 1-Antitrypsin/chemistry
• Neuroserpin

• Animals
• Animals, Genetically Modified
• History, 18th Century
• History, 19th Century
• History, 20th Century
• Humans
• Models, Molecular
• Prion Diseases/etiology
• Prion Diseases/history
• Prion Diseases/pathology
• Prion Diseases/physiopathology
• Prions/chemistry
• Prions/history
• Prions/immunology
• Protein Conformation
• Protein Isoforms/chemistry
• Protein Isoforms/history
• Yeasts