Brain Pathology

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Tau interacts with multiple heterogeneous nuclear ribonucleoproteins (hnRNPs)-a family of RNA binding proteins that regulate multiple known cellular functions, including mRNA splicing, mRNA transport, and translation regulation. We have previously demonstrated particularly significant interactions between phosphorylated tau and three hnRNPs (hnRNP A1, hnRNP A2B1, and hnRNP K). Although multiple hnRNPs have been previously implicated in tauopathies, knowledge of whether these hnRNPs colocalize with tau aggregates or show cellular mislocalization in disease is limited...

Non-neuroendocrine tumors account for around 10% of all primary neoplasms of the sella. If meningiomas, craniopharyngiomas, and germ cell tumors are excluded, the remaining lesions include a broad spectrum of uncommon, benign, and aggressive, often diagnostically challenging lesions. This review aims to summarize the essential clinicopathological features of tumors of the posterior pituitary gland, infundibulum spectrum expressing thyroid transcription factor 1, and primary sellar atypical rhabdoid teratoid tumor, and provide the criteria for their diagnosis and management...

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Schizophrenia (SZ) is a highly heritable mental disorder, and genome-wide association studies have identified the association between deleted in colorectal cancer (DCC) and SZ. Previous study has shown a lowered expression of DCC in the cerebral cortex of SZ patient. In this study, we identified novel single nucleotide polymorphisms (SNPs) of DCC statistically correlated with SZ. Based on these, we generated DCC conditional knockout (CKO) mice and explored behavioral phenotypes in these mice. We observed that deletion of DCC in cortical layer VI but not layer V led to deficits in fear and spatial memory, as well as defective sensorimotor gating revealed by the prepulse inhibition test (PPI)...

The majority of patients with Alzheimer's disease (AD) exhibit aggregates of Trans-active response DNA binding protein 43 (TDP-43) in their hippocampus, which is associated with a more aggressive disease progression. The TDP-43 inclusions are commonly found in neurons, but also in astrocytes. The impact of the inclusions in astrocytes is less known. In the current study, we investigate the presence of phosphorylated TDP-43 (pTDP-43) inclusions in astrocytic endfeet and their potential association with blood-brain barrier (BBB) damage, glymphatic system dysfunction, and AD pathology...

Three distinct MN1::BEND2 fusion-positive tumors in pediatric patients. (A) Clinical course for each patient was variable in part due to differences in initial diagnosis. Each patient responded favorably to gross total resection and is stable at last follow-up. (B) Histologic diversity, lack of prominent classical astroblastoma features, and variable immunoexpression of key markers makes microscopic diagnosis challenging.

The main genetic risk factors for Parkinson's disease (PD) are presently represented by variants in GBA1 gene encoding for the β-glucocerebrosidase (GCase). Searching for a peripheral biomarker that can be used for selecting and monitoring patients in clinical trials targeting GBA1-associated PD (GBA1-PD) is a current challenge. We previously demonstrated that α-synuclein oligomers expressed as proximity ligation assay (PLA) score in synaptic terminals of skin biopsy are a reliable biomarker for distinguishing idiopathic PD (iPD) from healthy controls (HC)...

The vast majority of pituitary neuroendocrine tumors (PitNETs) are benign and slow growing with a low relapse rate over many years after surgical resection. However, about 40% are locally invasive and may not be surgically cured, and about one percentage demonstrate an aggressive clinical behavior. Exceptionally, these aggressive tumors may metastasize outside the sellar region to the central nervous system and/or systemically. The 2017 (4th Edition) WHO Classification of Pituitary Tumors abandoned the terminology "atypical adenoma" for tumors previously considered to have potential for a more aggressive behavior since its prognostic value was not established...

Pituitary adenoma/pituitary neuroendocrine tumors (PitNETs) are the second most common primary intracranial tumor and the most frequent neuroendocrine tumors/neoplasms of the human body. Thus, they are one of the most frequent diagnoses in neuropathologist's practise. 2022 5th edition WHO Classification of Endocrine and Neuroendocrine Tumors does not support a grading and/or staging system for PitNETs and argues that histological typing and subtyping are more robust than proliferation rate and invasiveness to stratify tumors...

The evolution of classification systems of pituitary adenomas (now PitNETs) has culminated in the use of transcription factor (TF) immunohistochemistry (IHC), forming a cell lineage-based system. However, several issues remain to be addressed, including the additional financial and logistic burden of undertaking the complete array of anterior pituitary hormones and TF IHC. To that end, several groups have suggested algorithms to minimise the number of tests performed, with varying levels of diagnostic accuracy...

The major vascular cause of dementia is cerebral small vessel disease (SVD). Its diagnosis relies on imaging hallmarks, such as white matter hyperintensities (WMH). WMH present a heterogenous pathology, including myelin and axonal loss. Yet, these might be only the "tip of the iceberg." Imaging modalities imply that microstructural alterations underlie still normal-appearing white matter (NAWM), preceding the conversion to WMH. Unfortunately, direct pathological characterization of these microstructural alterations affecting myelinated axonal fibers in WMH, and especially NAWM, is still missing...

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Glioblastomas are aggressive brain tumors for which effective therapy is still lacking, resulting in dismal survival rates. These tumors display significant phenotypic plasticity, harboring diverse cell populations ranging from tumor core cells to dispersed, highly invasive cells. Neuron navigator 3 (NAV3), a microtubule-associated protein affecting microtubule growth and dynamics, is downregulated in various cancers, including glioblastoma, and has thus been considered a tumor suppressor. In this study, we challenge this designation and unveil distinct expression patterns of NAV3 across different invasion phenotypes...

No abstract text is available yet for this article.

Transmembrane and coiled-coil 2 (TMCC2) is a human orthologue of the Drosophila gene dementin, mutant alleles of which cause neurodegeneration with features of Alzheimer's disease (AD). TMCC2 and Dementin further have an evolutionarily conserved interaction with the amyloid protein precursor (APP), a protein central to AD pathogenesis. To investigate if human TMCC2 might also participate in mechanisms of neurodegeneration, we examined TMCC2 expression in late onset AD human brain and age-matched controls, familial AD cases bearing a mutation in APP Val717, and Down syndrome AD...

Hereditary cystatin C amyloid angiopathy (HCCAA) is an Icelandic disease that belongs to a disease class called cerebral amyloid angiopathy, a group of heterogenous diseases presenting with aggregation of amyloid complexes and deposition predominantly in the central nervous system. HCCAA is dominantly inherited, caused by L68Q mutation in the cystatin C gene, leading to aggregation of the cystatin C protein. HCCAA is a very progressive and severe disease, with widespread cerebral and parenchymal cystatin C and collagen IV deposition within the central nervous system (CNS) but also in other organs in the body, for example, in the skin...

Postoperative cognitive dysfunction (POCD) is a major concern, particularly among older adults. This study used social isolation (ISO) and multiomics analyses in aged mice to investigate potential mechanisms underlying POCD development. Aged mice were divided into two groups: ISO and paired housing (PH). Oleamide and the cannabinoid receptor type 2 (CB2R) antagonist AM630 were administered intraperitoneally, while Foxq1 adeno-associated viral (AAV) vector was injected directly into the hippocampus. Intramedullary tibial surgeries were subsequently performed to establish the POCD models...

Pituitary neuroendocrine tumour Ki-67 proliferation index varies according to the number of tumour cells assessed. Consistent Ki-67 scoring approaches and re-evaluation of the recommended Ki-67 3% cut-off are required to clarify controversies in pituitary neuroendocrine tumour Ki-67 proliferation index assessment.