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A quarter of a century ago, we proposed an innovative approach to study the pathogenesis of prion disease, one of the most intriguing biomedical problems that remains unresolved. The synthesis of a peptide homologous to residues 106‐126 of the human prion protein (PrP106‐126), a sequence present in the PrP amyloid protein of Gerstmann–Sträussler–Scheinker syndrome patients, provided a tractable tool for investigating the mechanisms of neurotoxicity. Together with several other discoveries at the beginning of the 1990s, PrP106‐126 contributed to underpin the role of amyloid in the pathogenesis of protein‐misfolding neurodegenerative disorders. Later, the role of oligomers on one hand and of prion‐like spreading of pathology on the other further clarified mechanisms shared by different neurodegenerative conditions. Our original report on PrP106‐126 neurotoxicity also highlighted a role for programmed cell death in CNS diseases. In this review, we analyse the prion research context in which PrP106‐126 first appeared and the advances in our understanding of prion disease pathogenesis and therapeutic perspectives 25 years later. [ABSTRACT FROM AUTHOR]

An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal degeneration (FTD) is the most common cause of dementia after Alzheimer's disease. To date, it has been addressed with intensive and intense research.Objective: To report on the most recent findings in the biology of FTD.Methods: Review of FTD literature.Results: FTD presents with many phenotypes that span from prefrontal syndromes to lower motor neuron disease passing through temporal, parietal and extrapyramidal syndromes. FTD includes the frontotemporal lobar atrophies clinically characterised by abnormal behaviour, progressive aphasia or semantic dementia, as well as corticobasal degeneration, progressive supranuclear palsy, progressive subcortical gliosis and FTD with motor neuron disease. The molecular classification of FTD can be traced following the immunocytochemical properties of the material accumulated in neuroectodermic cells. This procedure allows the separation of FTD with tau-positive inclusions from FTD with ubiquitin-positive inclusions, and from FTD with inclusions negative for both. Genetically, seven loci (chromosomes 3p, 9q and 17q24, one locus each; 9p and 17q21, two loci each) and four genes (MAPT, PRGN, VCP, CHMP2B) have been identified. Proteins involved are tau, progranulin, VCP, CHMP2B, Progranulin TDP43, ubiquitin and the intermediate neurofilament system. Neurodegeneration is most likely due to changes in cytoskeletal structure and in ubiquitin-dependent protein degradation activity. [ABSTRACT FROM AUTHOR]

In 9 patients with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) with a P301S tau mutation, the predominant phenotype was frontotemporal dementia in 3 and parkinsonism in 6. Comparison of the tau genotype/haplotype carrying the mutation and the initial clinical sign showed association between H1/H1 and parkinsonism and between H1/H2 and personality change. Thus, the tau haplotype carrying the mutation and the tau genotype may be related to the clinical phenotype throughout the disease course. [ABSTRACT FROM AUTHOR]

C.B., a right-handed 33-year-old man, presented with anterograde amnesiaafter acute heart block. Cognitive abilities were normal except for seriousimpairment of long-term episodic memory. The access to semantic informationwas fully preserved. Magnetic resonance showed high signal intensity and markedvolume loss in the hippocampus bilaterally; the left and right parahippocampalgyrus, lateral occipito–temporal gyrus, inferior temporal gyrus, andlateral temporal cortex were normal. This case underlines that global amnesiaassociated with hippocampal damage does not affect semantic memory. Althoughthe hippocampus is important in retrieving context-linked information, itsrole is not so crucial in retrieving semantic contents. Cortical areas surroundingthe hippocampus and lateral temporal areas might guide the recall of semanticinformation. [ABSTRACT FROM AUTHOR]

The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative diseases occurring in infancy and adulthood. Atypical forms of these diseases have been described and are particularly represented in the late-infantile and juvenile onset groups. Recent progress in biochemistry and molecular genetics has identified some of these variants as separate disease entities while disclosing the phenotypic variability of some classic forms. We report the result of a retrospective analysis performed on a series of 27 NCL patients, 15 of which were atypical as to clinical and/or pathological findings. Most of such patients, belonging to the late-infantile onset group and displaying homogeneous clinical-pathological features, were suggestive for CLN6. The two atypical juvenile NCL patients had features which resembled the “protracted form” of the disease. Given their relative frequency, strict clinical and pathological criteria are still the most useful tools for identifying and characterizing atypical forms and for defining phenotype-genotype correlations. [ABSTRACT FROM AUTHOR]

The neuropathological and neurochemical effects of intracisternally administered aluminum-powder suspensions were studied in adult rabbits. The right half of each brain was fixed for neuropathological examination, and neurotransmitter-synthesizing enzyme activities were measured in homogenates of structures dissected from the left half of each brain. The neuropathological changes associated with aluminum-induced encephalomyelopathy, including neurofibrillary degeneration, were observed in several regions of the central nervous system of the aluminum-treated rabbits. The striatum was consistently free of changes. Decreases in choline acetyltransferase and tyrosine hydroxylase activities of more than 30% were observed in the striatum of animals within 14-21 d and at longer times after aluminum injection. The decrease in striatal choline acetyltransferase activity appears to be unrelated to pathological changes in the striatal cholinergic neurons. The decrease in tyrosine hydroxylase activity in the striatum may be unrelated to neuropathological changes in dopaminergic cell bodies in the midbrain. Significant decreases in glutamate decarboxylase activity in the cerebellum may be related to cell losses in this region, whereas choline acetyltransferase activity deficits in the whole hippocampus remain unexplained. [ABSTRACT FROM AUTHOR]

Patients affected with Gerstmann-Sträussler-Scheinker disease from two families, one from Indiana and one of Swedish origin, have been studied. The patients are clinically characterized by cerebellar ataxia, extrapyramidal signs, and dementia. Accumulation of amyloid deposits and neurofibrillary tangles are the most conspicuous neuropathologic features. In the patients from the Indiana family, the amyloid contains an 11-kDa peptide, an amyloidogenic degradation product of the prion protein. The neurofibrillary tangles are composed of paired helical filaments and immunoreact with antibody to A68, an abnormally phosphorylated form of the microtubule-associated protein τ. In these families, the disease is caused by a point mutation in the PRNP gene. In the Indiana family the mutation ist at codon 198, and in the Swedish family at codon 217. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neurological derangement has been reported in haemodialysed patients receiving intravenous desferrioxamine (DFO) for aluminium-related disorders. The possible direct effects of desferrioxamine on EEG recordings were investigated in ten haemodialysed patients who underwent a DFO test 2 h after the end of dialysis. According to a commonly accepted protocol, 40 mg/kg body-weight of desferrioxamine was infused in 60 min. EEG recording was continuously performed, starting 30 min before and stopping 30 min after the desferrioxamine infusion. Besides visual inspection, EEG records were digitised, tapered, and spectrally analysed with Digital PDP 11/73 microcomputer. Basal EEG recording was normal in all patients. In three patients a progressive EEG slowing was detected by visual inspection during desferrioxamine infusion; in these cases automatic analysis revealed a 50% increase in power of slower frequencies 30 min after starting the infusion, when no changes in plasma aluminium concentrations are detected; a complete recovery was observed 30 min after desferrioxamine withdrawal. In one patient bilateral paroxysms of slow waves appeared, so we stopped desferrioxamine infusion. Two of the three patients who developed EEG abnormalities also had an increased aluminium body burden (positive DFO test).Results indicated that desferrioxamine per se can modify EEG in haemodialysis patients and that its effect is not mediated by acute increases of plasma aluminium concentrations. The finding of a positive DFO test in two of three patients with EEG changes may suggest that an aluminium-induced blood-brain barrier derangement could have played a role. However, prompt recovery after ceasing desferrioxamine infusion strongly suggests a direct role of desferrioxamine in the induction of EEG changes. These findings contribute to a better understanding of the acute impairment in neurological status when high doses of desferrioxamine are infused in haemodialysis patients with aluminium overload. [ABSTRACT FROM PUBLISHER]

Copyright of Journal of Neurology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dementia is due to lesions destroying a large amount of circuits anatomically connected with, or functionally related to, the associative areas of the cortex and the limbic structures. Dementia is not only the clinical hallmark of neurodegenerative diseases, most often proteinopathies, primarily involving the cerebral cortex, but also a symptom frequently associated to movement disorders, or secondary to systemic or neurological, non-degenerative diseases. In the elderly, it is often the consequence of the cumulative effect of different diseases. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cerebral amyloid angiopathy is due to β-protein accumulation in the vessel walls and occurs in normal aging, Alzheimer’s disease and hereditary cerebral hemorrhage with amyloidosis. It causes intraparenchimal and subarachnoid bleeding with hemosiderin deposits and multiple infarcts presenting with headache, stroke and epilepsy. Such lesions may contribute to cognitive impairment. So far, no therapy is available. In future, amyloid in the vessel wall might be addressed by amyloid disaggregating drugs and amyloid antibodies. [ABSTRACT FROM AUTHOR]