Free neuropathology最新文献

{"title":"Multiple sclerosis: 2026 update.","authors":"Luisa Klotz, Mike P Wattjes, Tanja Kuhlmann","doi":"10.17879/freeneuropathology-2026-9705","DOIUrl":"10.17879/freeneuropathology-2026-9705","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is the inflammatory-demyelinating disease of the CNS with the highest prevalence. Despite significant progress in reducing relapse activity by immunomodulatory or immunosuppressive treatments, there are ongoing challenges in understanding its initiation and predicting disease evolution. Furthermore, since we only partially understand the mechanisms driving disease progression, its successful treatment represents a major challenge. Therefore, this review article summarizes key research findings from the last 18 months, covering advances in the understanding of pathophysiology including the effects of aging on glial and immune cells as well as the functional role of tissue-resident memory cells. Additionally, we discuss advances in imaging technologies and biomarkers as well as the use of AI to predict disease evolution. Finally, we report the most recent findings from clinical trials targeting immune cells within the CNS.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2026-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain extraction for fixed tissue banking: a technical report.","authors":"Mads Wolf, Autumn Beck, Laura Paredes, Sarah Darcy, Alexander Parra, Gabriel A Taylor, Macy Garrood, Emma L Thorn, Claudia De Sanctis, John F Crary, Kurt Farrell, Andrew T McKenzie","doi":"10.17879/freeneuropathology-2026-9411","DOIUrl":"10.17879/freeneuropathology-2026-9411","url":null,"abstract":"<p><p>Brain banking enables the study of human neural tissue and is essential for research on disease, physiology, and neuroanatomy. An essential step for whole brain studies is the extraction of the brain from the skull. Yet detailed technical descriptions of brain removal are rare, perhaps contributing to the artifactual tissue disruption sometimes observed as a result of the procedure. Here, we describe a method for whole brain extraction that could be implemented in the context of a whole-body donation, focused on the use case of fixed tissue banking. The method involves a sequential craniectomy that uses both circumferential and midline sagittal cuts, followed by a posterior approach to cutting the dura. We report the application of this protocol across n = 105 human whole-body donors. We document the time required for each procedural step and the frequency of craniectomy artifacts and skull edge artifacts at the brain surface. When the brain tissue is particularly soft, we also describe the potential use of <i>in situ</i> immersion fixation to increase tissue stiffness before removal, finding however that this also slows the diffusion of chemicals into the interior of the brain. Our experience suggests that the effectiveness of brain extraction can be improved via procedural optimizations. Technicians can become comfortable with the method after approximately 5-10 cases. We anticipate that improving brain extraction quality may support downstream work in the development of diagnostics and treatments for neurological and psychiatric disease.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13217454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148139917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forensic neuropathology: 2026 update.","authors":"Jakob Matschke","doi":"10.17879/freeneuropathology-2026-9343","DOIUrl":"10.17879/freeneuropathology-2026-9343","url":null,"abstract":"<p><p>This review discusses key publications in forensic neuropathology from the 2025 literature. In abusive head trauma (AHT), biomechanical models help clarify injury mechanisms, particularly the role of sagittal angular acceleration in younger infants. However, challenges remain, such as detecting subtle brainstem pathology with neuroimaging, stressing the need for prospective clinicopathological correlation. Meanwhile, understanding of chronic traumatic encephalopathy (CTE) is expanding beyond contact sports to include victims of intimate partner violence. Research on sudden unexpected death in epilepsy (SUDEP) indicates overlaps with sudden infant death syndrome (SIDS) and identifies key risk factors. At the same time, forensic neuropathology's primary role remains the exclusion of other causes of death. Artificial intelligence shows promise for analyzing radiological and histopathological data in traumatic brain injury (TBI) and epilepsy, though its adoption for routine purposes remains a distant goal. Further developments include a better understanding of the cerebellum's vulnerability to TBI, standardized postmortem MRI protocols, and the use of cerebrospinal fluid biomarkers, such as GFAP and S100B, to estimate time of death. Finally, research continues to probe the complex links between brain morphology and behavior, and recent studies of the neuropathology of alcohol use disorder have revealed microglial changes rather than overt neuronal loss.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometry imaging-based explainable machine learning reveals the biochemical landscapes of the mouse brain.","authors":"Jacob Gildenblat, Jorunn Stamnas, Jens Pahnke","doi":"10.17879/freeneuropathology-2026-9413","DOIUrl":"10.17879/freeneuropathology-2026-9413","url":null,"abstract":"<p><p>Recent computational advances in mass spectrometry imaging (MSI) now enable unprecedented insight into organ-wide molecular composition and functional architecture. Here, we present the first high-resolution molecular-computational atlas of specific mouse brain lipids and metabolites, acquired using a NEDC matrix and negative-mode MSI, covering 123 anatomically defined regions and 191 polygonal annotations derived solely from MSI data, without auxiliary imaging. To overcome annotation ambiguity and MSI complexity, we introduced the <i>Computational Brain Lipid Atlas</i> (CBLA), a graph-based visual-explainability framework that generates <i>Virtual Landscape Visualizations</i> (VLVs) of specific lipid distributions across brain substructures. The CBLA integrates dimensionality reduction and ensembles of supervised models to (i) refine annotations, (ii) elucidate interregional relationships, (iii) interpret model behavior, and (iv) formulate biologically testable hypotheses. The CBLA revealed novel lipid distribution patterns, functional integrations, anatomical connections - the brain's telephone cables, and region-specific disease signatures - index lipids, including disease networks in the basal ganglia. It further identified index lipids that trace extrapyramidal nuclei and their cortical-brainstem connections, highlighting network-level molecular organization. A new algorithm decomposes annotated regions into precise mass-to-charge (<i>m/z)</i> features and resolves high-resolution <i>m/z</i> values from MSI data, <i>m/z</i> producing a comprehensive high-resolution brain map. It can be applied to any MS measurements, including metabolites, lipids, and peptides. This resource underpins downstream studies, as exemplified here by characterizing the molecular lipid composition of Aβ plaques in APP and ABCA7 transgenic mice, their spatial arrangement, and their connections with surrounding tissue. For the first time, our data suggest that GM3 ganglioside accumulation in cortical amyloid plaques may originate from hippocampal structures, consistent with longstanding evidence of disrupted hippocampo-cortical connectivity; a similar origin may also apply to plaque-associated Aβ signals in the cortex. More broadly, several selected <i>m/z</i> signals showed putative anatomical origins in specific brain subregions. Together, these findings establish MSI-ATLAS as a general framework for mapping brain organization and disease-related molecular networks directly from MSI data.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral optic perineuritis with vestibulocochlear involvement: revisiting a rarely performed biopsy.","authors":"Katrina J Jiang, Marianne E Yassa, Saad Awan, Osama R Elkadi","doi":"10.17879/freeneuropathology-2026-9407","DOIUrl":"10.17879/freeneuropathology-2026-9407","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13073701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why it should be \"Alzheimer disease\" rather than \"Alzheimer's disease\".","authors":"Cinthya Aguero, C Zachary Klein, Georg Haase","doi":"10.17879/freeneuropathology-2026-9132","DOIUrl":"10.17879/freeneuropathology-2026-9132","url":null,"abstract":"<p><p>The terms \"Alzheimer's disease\" and \"Alzheimer disease\" are often used interchangeably in the biomedical literature. Yet this seemingly minor grammatical difference carries implications that extend beyond style: the possessive form, marked by the 's eponym, may imply ownership of a disease by an individual, a notion discouraged by several authoritative medical style guides and international health organizations [1]. In this article, we examine the historical emergence of the term \"Alzheimer's disease\", analyze the trajectories of the possessive and non-possessive eponyms in PubMed-indexed article titles from 1950 to 2025, and assess how the choice of terminology influences literature retrieval. Our analysis indicates that the possessive form has overwhelmingly dominated the literature for decades. However, searches using \"Alzheimer's disease\" or \"Alzheimer disease\" retrieve non-identical, only partially overlapping sets of records in PubMed. We argue that adopting the non-possessive form \"Alzheimer disease\" would improve conceptual clarity, terminological consistency, and the completeness of literature retrieval, particularly in systematic reviews and meta-analyses.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13015839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust immunohistochemical detection of α-synuclein, tau and amyloid-β in human brain tissue archived for up to 78 years.","authors":"Mie Kristine Just, Kristina Bang Christensen, Martin Wirenfeldt, Torben Steiniche, Laura Parkkinen, Liisa Myllykangas, Per Borghammer","doi":"10.17879/freeneuropathology-2026-9375","DOIUrl":"10.17879/freeneuropathology-2026-9375","url":null,"abstract":"<p><p><b>Objective</b>: Brain branks preserve extensive material relevant to neurodegenerative disease research. As these collections age, tissue becomes archival, raising the question of whether long-term fixed and stored human brain tissue remains suitable for contemporary immunohistochemical analyses. <b>Materials and Methods</b>: Forty-one autopsy brains collected between 1946 to 1980 were examined. For each case, midbrain and hippocampus were available both as original paraffin-embedded blocks and as tissue stored long term in fixative. New paraffin blocks were prepared from the long-term fixated tissue. Sections from original and newly prepared blocks were immunohistochemically stained for α-synuclein, hyperphosphorylated tau and amyloid-β. Immunoreactivity was assessed using semi-quantitative scoring. <b>Results</b>: Original blocks consistently showed good staining intensity and morphological preservation for each protein pathology. Newly prepared blocks showed slightly lower semi-quantitative scores for Lewy-related pathology, without statistically significant differences, except for astrocytic α-synuclein in the substantia nigra in cases from the 1960s. Tau pathology displayed modestly reduced labelling, particularly of the neuropil threads and neurofibrillary tangles, most evident in cases from the 1950s. Amyloid-β-positive senile plaques showed similar or slightly higher scores in newly prepared blocks, with no significant differences across regions. <b>Conclusion</b>: Human brain tissue preserved as paraffin-embedded blocks or stored in fixative for up to 78 years remains suitable for immunohistochemical analyses. Adequate-to-good detection of aggregated α-synuclein, hyperphosphorylated tau and amyloid-β is achievable, indicating preserved pathological hallmarks of Lewy Body Disease and Alzheimer's Disease in archival tissue.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reflections on a long career in Neuropathology.","authors":"Michael Farrell","doi":"10.17879/freeneuropathology-2026-9304","DOIUrl":"10.17879/freeneuropathology-2026-9304","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Form follows function: morphology as a map of mechanisms in neurodegenerative disease pathology.","authors":"Edward B Lee","doi":"10.17879/freeneuropathology-2026-9241","DOIUrl":"https://doi.org/10.17879/freeneuropathology-2026-9241","url":null,"abstract":"<p><p>Across neurodegenerative diseases, the shape and spatial organization of pathology carry rich mechanistic information. Vacuoles, spongiosis, oligodendroglial coiled bodies, dendritic dystrophic neurites, amyloid plaque compactness, and phase-separated droplets each reflect distinct cellular identities, subcellular compartments, trafficking pathways, and biophysical material states. Here, I synthesize morphological signatures across neurodegenerative diseases to propose a framework that links morphology to mechanism. Morphology is neither incidental nor merely descriptive. Rather, it is a readout of the basic mechanisms that govern self-assembly of proteins into aggregates, the cell's attempts at proteostasis (clearance, sequestration, and transport), and the failure that ensues.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12825461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The shapes of brain waste: Mysteries of cellular remnant morphology in neurodegeneration.","authors":"David V Forrest","doi":"10.17879/freeneuropathology-2026-9059","DOIUrl":"10.17879/freeneuropathology-2026-9059","url":null,"abstract":"<p><p>This meditation with apologies by a psychiatrist who is not a neuropathologist but attends CPCs of movement disorder patients speculates about how microscopic mechanical processes produce the variety of cellular neuropathological forms, which differ with diagnoses, and wonders what may be revealed by the shapes of these traces by future neuropathologists. New discoveries about tiny machines, nanotubules and the like only increase the intrigue and possibilities of revelations, likened to a crime scene investigation.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"7 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}