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R Crook

Publications and source records attributed to R Crook.

At least 19 recordsLinked to original sources
PubMed2006

Conductance quantization at a half-integer plateau in a symmetric GaAs quantum wire.

We present data from an induced gallium arsenide (GaAs) quantum wire that exhibits an additional conductance plateau at 0.5(2e2/h), where e is the charge of an electron and h is Planck's constant, in zero magnetic field. The plateau was most pronounced when the potential landscape was tuned to be symmetric by using low-temperature scanning-probe techniques. Source-drain energy spectroscopy and temperature response support the hypothesis that the origin of the plateau is the spontaneous spin-polarization of the transport electrons: a ferromagnetic phase. Such devices may have applications in the field of spintronics to either generate or detect a spin-polarized current without the complications associated with external magnetic fields or magnetic materials.

Journal Article↗
PubMed2004

Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy.

OBJECTIVE: To examine the clinical, genetic, and neuropathologic features of posterior cortical atrophy (PCA). DESIGN/METHODS: Using a broad definition of PCA as a syndrome with the insidious onset of visual dysfunction in the absence of primary ophthalmologic causes, the authors identified and then reviewed the presenting signs and symptoms, ApoE genotypes, tau haplotypes, and neuropathologic findings when available of PCA cases from two dementia research centers collected over the past 14 years. RESULTS: The authors identified 40 PCA cases. Their mean age at symptom onset was 60.5 +/- 8.9 years. There were twice as many women as men in the series. The principal types of visual impairment were simultanagnosia (82%) and visual field defect (47.5%). Acalculia, alexia, and anomia were also common. Insight was preserved in almost all (95%) early in the disorder. Neither apoE epsilon4 nor tau haplotype frequencies were different from typical Alzheimer disease (AD). Nine patients had died and underwent postmortem examination. Seven autopsied cases had AD pathology but when compared to typical AD, the neurofibrillary tangle (NFT) densities were significantly higher in Brodmann areas 17 and 18 (p < 0.05) and significantly lower in the hippocampus (p < 0.05). Two cases had corticobasal degeneration with maximal involvement of tau positive glial pathology in the posterior parietal lobe and Brodmann areas 17 and 18. CONCLUSIONS: PCA is a distinctive dementia syndrome in which the most pronounced pathologic involvement is in the occipitoparietal regions independent of the specific underlying pathology. AD was the most common pathologic cause, but its regional distribution differed from typical AD.

Adult↗
PubMed2003

Imaging fractal conductance fluctuations and scarred wave functions in a quantum billiard.

We present scanning-probe images and magnetic-field plots which reveal fractal conductance fluctuations in a quantum billiard. The quantum billiard is drawn and tuned using erasable electrostatic lithography, where the scanning probe draws patterns of surface charge in the same environment used for measurements. A periodicity in magnetic field, which is observed in both the images and plots, suggests the presence of classical orbits. Subsequent high-pass filtered high-resolution images resemble the predicted probability density of scarred wave functions, which describe the classical orbits.

Journal Article↗
PubMed2001

A novel presenilin mutation (M233V) causing very early onset Alzheimer's disease with Lewy bodies.

Presenilin 1 mutations are the major cause of autosomal dominant Alzheimer's disease: here we identify a new missense mutation causing a methionine to valine change at codon 233. This codon is homologous to a pathogenic presenilin 2 mutation with the same base change (ATG to GTG) and amino acid change (M239V). This mutation causes disease with an exceptionally early onset age (approximately 30 years) in which pathological examination shows extensive Lewy bodies as well as plaques and tangles.

Adult↗
PubMed2001

Presenilin mutations line up along transmembrane alpha-helices.

Presenilin 1 mutations are the major cause of autosomal dominant Alzheimer's disease. Here we present evidence that pathogenic mutations in putative transmembrane domains 1, 2, 3, 4 and 6 align along helical faces, thus supporting the view that these are indeed transmembrane domains, and suggesting that disruption of the alignment of these domains is responsible for the pathogenicity of the mutations.

Humans↗
PubMed2001

Genetic analysis of synphilin-1 in familial Parkinson's disease.

alpha-Synuclein is present in Lewy bodies of patients with both sporadic and familial Parkinson's disease. However, pathogenic mutations Ala30Pro and Ala53Thr in alpha-synuclein are rare causes of disease. Synphilin-1 has been demonstrated to associate with alpha-synuclein and promote the formation of cytosolic inclusions in vitro. Two-point genetic linkage analysis of a dinucleotide repeat within the synphilin-1 gene initially implicated this locus as a cause of Parkinson's disease in three of nine families. However, subsequent haplotype, sequencing, and association analyses in these three families and an independent case-control series suggest that variability within the locus does not confer susceptibility to Parkinson's disease.

Aged↗
PubMed2001

Cotton wool plaques in non-familial late-onset Alzheimer disease.

Cotton wool plaques (CWP) are large, ball-like plaques lacking dense amyloid cores that displace adjacent structures. They were first described in a Finnish kindred with early-onset Alzheimer disease (AD) with spastic paraparesis due to a presenilin-1 delta9 mutation. We describe a case of sporadic late-onset AD with numerous neocortical CWP as well as severe amyloid angiopathy and marked leukoencephalopathy, compared with 16 cases of late-onset AD with similar degrees of amyloid angiopathy and leukoencephalopathy. The cases were studied with histologic methods and with single and double immunostaining for beta-amyloid (Abeta), paired helical filaments-tau (PHF-tau), neurofilament (NF), glial fibrillary acidic protein (GFAP), HLA-DR, and amyloid precursor protein (APP). We found that CWP were well-circumscribed amyloid deposits infiltrated by ramified microglia and surrounded by dystrophic neurites that were immunopositive for APP, but only weakly for NF and PHF-tau. Abeta1-12 was diffuse throughout the CWP, while Abeta37-42 was peripherally located and Abeta20-40 more centrally located. Two of the 16 late-onset AD cases also had CWP, but they were also admixed with diffuse plaques and plaques with dense amyloid cores. Pyramidal tract degeneration was not a consistent finding or a prominent feature in any case. The results suggest that CWP are not specific for early-onset familial AD with spastic paraparesis.

Age of Onset↗
PubMed2000

Susceptibility locus for Alzheimer's disease on chromosome 10.

The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci. Here we report evidence for an Alzheimer's disease locus on chromosome 10. Our stage one multipoint lod score (logarithm of the odds ratio for linkage/no linkage) of 2.48 (266 sibling pairs) increased to 3.83 in stage 2 (429 sibling pairs) close to D10S1225 (79 centimorgans). This locus modifies risk for Alzheimer's disease independent of APOE genotype.

Age of Onset↗
PubMed2000

Variant Alzheimer's disease with spastic paraparesis: clinical characterization.

OBJECTIVE: To present the clinical, neuroimaging, and electrophysiologic characteristics of a variant AD phenotype. BACKGROUND: The authors have identified a large Finnish kindred with presenile dementia and spastic paraparesis due to deletion of exon 9 of presenilin 1. Neuropathologic analysis showed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyloid peptide but lacking congophilic cores. PATIENTS AND METHODS: Twenty-two affected individuals (16 men and 6 women) were identified in four successive generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine deceased patients were evaluated. Electrophysiologic investigations were available in eight cases. CT or MRI of the head had been performed on 11 patients and PET was performed on three patients. RESULT: The mean age at onset (+/-SD) was 50.9 +/- 5.2 years (range 40 to 61 years). Memory impairment was present in all patients. Memory impairment appeared simultaneously with or was preceded by walking difficulty due to spasticity of the lower extremities (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14) in some patients suggested cerebellar involvement. EEG showed intermittent generalized delta-theta activity. Head MRI showed temporal and hippocampal atrophy; PET showed bilateral temporo-parietal hypometabolism. CONCLUSION: Spastic paraparesis or brisk stretch reflexes of lower extremities or clumsiness of hands combined with dementia suggests this variant of AD.

Age of Onset↗
PubMed2000

Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations.

We describe 3 new families affected by Alzheimer's disease with spastic paraparesis. In affected individuals, including the earliest known patient with this clinical syndrome, neuropathological examination revealed large "cotton wool" plaques similar to those we have previously described in a Finnish family. In the families in which DNA was available, presenilin-1 mutations were observed. Transfection of cells with these mutant genes caused exceptionally large increases in secreted Abeta42 levels. Furthermore, brain tissue from individuals with this syndrome had very high amyloid-beta concentrations. These findings define the molecular pathogenesis of an important subgroup of Alzheimer's disease and have implications for the pathogenesis of the disease in general.

Alzheimer Disease↗
PubMed1999

Neurodegenerative diseases of Guam: analysis of TAU.

Mutations in the tau gene have been described in families affected by frontotemporal dementia with parkinsonism linked to chromosome 17. The authors performed a genetic and biochemical analysis of this gene and its product in the parkinsonism dementia complex of Guam, a disorder characterized by the extensive formation of neurofibrillary tangles. The tau gene is not a primary cause of the parkinsonism dementia complex of Guam.

Aged↗
PubMed1999

Genetic variability at the amyloid-beta precursor protein locus may contribute to the risk of late-onset Alzheimer's disease.

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 flanking microsatellite repeat markers: thus we have used APP-PCR3 and D21S210 to examine the segregation of the amyloid-beta precursor protein (APP) gene, the markers DI 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 identification of genetic risk loci is relatively insensitive as indicated by the failure of the ApoE locus to reach statistical significance (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 confirmation in other series of familial cases.

Age of Onset↗
PubMed1999

No pathogenic mutations in the beta-synuclein gene in Parkinson's disease.

We present 11 families consistent with autosomal dominant inheritance of probable Parkinson's disease (PD). Although excluded as a cause of disease in these kindreds, mutations in the alpha-synuclein gene have been implicated in familial PD. The beta-synuclein gene is highly homologous, expressed in the nervous system and thus is a good candidate gene for PD. Multipoint linkage analysis was either equivocal or excluded 5q35 haplotype sharing among affected family members. Sequencing the translated exons of the beta-synuclein gene failed to identify any pathogenic mutation.

Adult↗
PubMed1999

A novel candidate presenilin-1 interacting protein containing tetratricopeptide repeats.

The yeast two-hybrid system, immunofluorescence and co-immunoprecipitation techniques were used to identify a novel candidate protein with which presenilin-1 (PS-1) interacts. This interacting protein, the gene of which is encoded on chromosome 16, contains two tetratricopeptide repeats (TPR) that are known to mediate interactions between proteins, appears to be primarily localized to the cytoplasm of transfected HEK293 cells, and is expressed in brain. Preliminary yeast two-hybrid data suggests this candidate may interact with both heat shock protein-90 and heat shock protein-70 and thus may be a novel member of TPR-containing proteins which interact with this complex.

Alzheimer Disease↗
PubMed1999

No association between the alpha-2 macroglobulin I1000V polymorphism and Alzheimer's disease.

Recent reports have suggested that variability in the alpha2-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.

Age of Onset↗
PubMed1999

Association between coding variability in the LRP gene and the risk of late-onset Alzheimer's disease.

We have sequenced the entire (89 exons) open reading frame of the LRP gene in 12 cases of Alzheimer's disease (AD) from Northern France. We have found no novel changes but confirm the occurrence of a polymorphism in exon 6 of the gene (A216V). This polymorphism is rare (2.8% of controls) and is in linkage equilibrium with previously reported polymorphisms. The V216 allele is negatively associated with the disease in a large case-controlled series. These data suggest that the LRP receptor may be involved in the pathobiology of AD, but the association that we report here cannot explain the previously reported genetic data implicating the LRP gene in AD. If the LRP gene is a major site of genetic variability leading to AD, there must be other biologically relevant variability in promoter or other regulatory elements of this large gene.

Aged↗