Hans A. Kretzschmar

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Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic(More)
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(More)
Assessment of Alzheimer’s disease (AD)-related neurofibrillary pathology requires a procedure that permits a sufficient differentiation between initial, intermediate, and late stages. The gradual deposition of a hyperphosphorylated tau protein within select neuronal types in specific nuclei or areas is central to the disease process. The staging of(More)
OBJECTIVE Amyotrophic lateral sclerosis (ALS) is a common, fatal motor neuron disorder with no effective treatment. Approximately 10% of cases are familial ALS (FALS), and the most common genetic abnormality is superoxide dismutase-1 (SOD1) mutations. Most ALS research in the past decade has focused on the neurotoxicity of mutant SOD1, and this knowledge(More)
Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. The neuropathology associated with most FTD is characterized by abnormal cellular aggregates of either transactive response DNA-binding protein with Mr 43 kDa (TDP-43) or tau protein. However, we recently described a subgroup of FTD patients, representing around 10%,(More)
Expansion of a GGGGCC hexanucleotide repeat upstream of the C9orf72 coding region is the most common cause of familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTLD/ALS), but the pathomechanisms involved are unknown. As in other FTLD/ALS variants, characteristic intracellular inclusions of misfolded proteins define C9orf72(More)
The normal cellular form of prion protein (PrPC) is a precursor to the pathogenic protease-resistant forms (PrPSc) believed to cause scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease. Its amino terminus contains the octapeptide PHGGGWGQ, which is repeated four times and is among the best-preserved regions of mammalian PrPC. Here(More)
TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed ubiquitin and TDP-43(More)
Pathologic TAR-DNA-binding protein 43 (TDP-43) is a disease protein in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis. We studied the presence, frequency, and distribution of TDP-43 pathology by immunohistochemistry and biochemistry in a series of clinically well-characterized tauopathy(More)
Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc. Here we describe a monoclonal(More)