Neurocysticercosis is a neurologic parasitic disease caused by the encysted larva of the tapeworm Taenia solium and is the most important parasitic disease of the human central nervous system. It is the most common cause of acquired epilepsy in endemic settings and constitutes a public health challenge for most of the developing world. Nowadays, however, as a result of globalization, neurocysticercosis is being seen more frequently in developed countries as well. Neurocysticercosis is acquired through fecal-oral contamination, and the disease course is complex, with two intermediate hosts (ie, pigs and humans) and a definitive host (humans). Traditionally, it has been classified into active and nonactive forms according to disease location. Radiologists must be aware of its imaging appearance, which is quite variable, as is the differential diagnosis. Imaging findings depend on several factors, including the stage of the life cycle of T solium at presentation; the number and location (ie, subarachnoid, cisternal, or intraventricular) of parasites; and associated complications such as vascular involvement (ie, arteritis with or without infarction), inflammatory response (ie, edema, gliosis, or arachnoiditis), and, in ventricular forms, degree of obstruction. Thus, the diagnostic approach, management, and prognosis for neurocysticercosis differ widely depending on the type of infection.

Neurofibrillary tangles (NFT) and dystrophic neurites represent dense cytoplasmic accumulations of abnormal polymers in the brain of patients with Alzheimer's disease (AD). These polymers are referred to as paired helical filaments (PHFs) whose main structural core is composed of tau protein. Tau processing has been associated with hyperphosphorylation and truncation that results in PHF assembly. Both molecular events appear to cause conformational change of tau molecules [11,17,32]. In this regard, in a previous work focused on the analysis of patterns of immunolabeling in pre-tangle cells, we found that regional changes precede the structural modifications in tau [32]. In the present study, we further analyzed the early stages of tau processing in pre-tangle cells by using a variety of immunological markers of specific N-terminus phosphorylation tau sites. We used AT100, TG-3, AT8, pT231, Alz-50, Tau-C3 and 423 antibodies that recognize different abnormal tau epitopes in AD brains. These antibodies were combined and analyzed using a confocal microscope. Our results indicate that the early stages of abnormal tau processing are characterized by a sequential appearance of specific phospho-dependent epitope. The cascade of appearance of the antibodies is: pT231→TG-3→AT8→AT100→Alz-50. In addition; truncation at Asp-421 of the C-terminus of tau protein, as detected by Tau-C3, is also an early molecular event in tau protein aggregation prior to PHF formation in AD.

Neurofibrillary tangles (NFTs) are the neuropathological hallmarks in Alzheimer's disease (AD). Densities of NFTs correlate with the dementia status. NFTs reflect the intracellular accumulation of abnormal paired helical filaments (PHFs) composed of the microtubule-associated protein tau. Hyperphosphorylation and truncation have been proposed as key events leading to the genesis of PHFs. A recent hypothesis involving conformational changes has been emerging. These structural modifications of the tau protein were detected by monoclonal antibodies (mAbs) recognizing discontinous epitopes along the tau molecule such as Alz-50, Tau-66 and MC1. A new mAb, TG-3, detects an early pathology in AD. The epitope of mAb TG-3 maps to phosphorylated Thr 231 when the tau molecule is conformationally altered. In the present study, we used confocal microscopy to analyze the state of tau molecule adopting the TG-3 conformation during tangle formation. We also compared mAb TG-3 immunoreactivity with that of mAb Alz-50. Immunoelectronmicroscopy was also performed. N-and C-termini markers evidenced that the tau molecule is intact when it adopts the TG-3 conformation. In addition to NFT, mAb TG-3 also recognized NFT-not bearing-neurons suggesting an early processing of tau prior to NFT formation. Ultrastructural analysis evidenced the presence of TG-3 and Alz-50 immunoreactive products on organelles including mitochondria and endoplasmic reticulum. Nuclear heterochromatin was densely immunolabelled. These results together with the fact that TG-3 immunoreactivity is related to intact tau suggest that the conformation recognized by TG-3 is early staged in the neuronal pathology of AD. In addition, we document that the earliest changes in tau occur closely associated with organelles and heterochromatin.

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.