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- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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- Sundal, Christina, et al.
(författare)
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Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations
- 2013
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020. ; 19:10, s. 869-877
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Tidskriftsartikel (refereegranskat)abstract
- Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by noninflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We studied neuropathologically verified HDLS patients with CSF1R mutations to assess parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18-71) and the mean disease duration was approximately six years (range, 3-11). We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations.
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- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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- Kovacs, Gabor G., et al.
(författare)
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Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy
- 2016
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:1, s. 87-102
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Tidskriftsartikel (refereegranskat)abstract
- Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
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- Björk, Linnea, et al.
(författare)
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Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene‐Vinylene‐Based Ligands towards Aβ or Tau Pathology in Alzheimer's Disease
- 2023
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 26:41, s. e202300583-
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Tidskriftsartikel (refereegranskat)abstract
- Distinct aggregated proteins are correlated with numerous neurodegenerative diseases and the development of ligands that selectively detect these pathological hallmarks is vital. Recently, the synthesis of thiophene-based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs), that could be utilized for selective assignment of tau pathology in brain tissue with Alzheimer's disease (AD) pathology, was reported. Herein, we investigate the ability of these ligands to selectively distinguish tau deposits from aggregated amyloid-β (Aβ), the second AD associated pathological hallmark, when replacing the terminal thiophene moiety with other heterocyclic motifs. The selectivity for tau pathology was reduced when introducing specific heterocyclic motifs, verifying that specific molecular interactions between the ligands and the aggregates are necessary for selective detection of tau deposits. In addition, ligands having certain heterocyclic moieties attached to the central thiophene-vinylene building block displayed selectivity to aggregated Aβ pathology. Our findings provide chemical insights for the development of ligands that can distinguish between aggregated proteinaceous species consisting of different proteins and might also aid in creating novel agents for clinical imaging of tau pathology in AD.
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- Ghetti, R, et al.
(författare)
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Characterization of nuclear sources via two-neutron intensity interferometry
- 1999
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Ingår i: NUCLEAR PHYSICS A. - : ELSEVIER SCIENCE BV. - 0375-9474. ; 660:1, s. 20-40
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Tidskriftsartikel (refereegranskat)abstract
- The neutron energy spectrum and the two-neutron correlation function have been measured for the E/A = 45 MeV Ni + Al reaction in order to assess the space-time characteristics of the neutron emitting source. When comparing the data to a statistical model,
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| 26. |
- Ghetti, R, et al.
(författare)
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Influence of cross-talk rejection procedures on two-neutron intensity interferometry.
- 1999
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 421:3, s. 542-551
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the effects of a cross-talk rejection procedure on the two-neutron correlation function. The rejection method relies only upon simple kinematic relations between the energy of the detected neutrons and can be applied to commonly used detector configurations. It is demonstrated that the comparison of a cross-talk corrected correlation function with the theory is meaningful as long as the cross-talk rejection procedure and the response of the detector filter are consistently incorporated into the theoretical calculations.
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| 27. |
- Ghetti, R., et al.
(författare)
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Influence of multiple sources on the two-neutron correlation function in Ni-induced, intermediate energy, heavy ion reactions
- 2001
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Ingår i: Physical Review C. Nuclear Physics. - : American Physical Society. - 0556-2813 .- 1089-490X. ; 64:1
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Tidskriftsartikel (refereegranskat)abstract
- The strength of the neutron-neutron correlation function from the E=45AMeV58Ni+27Al, natNi, and 197Au reactions depends on the neutron parallel velocity. This indicates the presence of multiple sources of neutron emission. We find these sources consistent with a dissipative, binary reaction mechanism as it is described by, e.g., Boltzmann-Uehling-Uhlenbeck calculations.
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| 37. |
- Urrata, M, et al.
(författare)
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Neutron-neutron Intensity Interferometry in E/A = 45 MeV 58Ni + 27Al, 58Ni and 197Au Reactions
- 2000
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Ingår i: Physical Review C. Nuclear Physics. - : American Institute of Physics (AIP). - 0556-2813 .- 1089-490X. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- Small angle neutron-neutron correlations have been measured for the E/A=45 MeV 58Ni+27Al, natNi, and 197Au reactions. Two-neutron correlation functions, both integrated and gated on the total momentum of the neutron pair, have been constructed. In order to explain these data, a fraction of fast "dynamical" emission is needed in addition to slower evaporative emission. The overall emission time scale is shorter for the symmetric system, indicating that the dynamical component is stronger in this case.
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