Neuropathology and Applied Neurobiology最新文献

{"title":"Diagnostic Challenges in Choroid Plexus Tumours.","authors":"Christian Thomas, Martin Hasselblatt","doi":"10.1111/nan.70095","DOIUrl":"10.1111/nan.70095","url":null,"abstract":"<p><p>Choroid plexus tumours are rare epithelial neoplasms arising from the choroid plexus, accounting for approximately 0.2% of all central nervous system tumours but up to 20% of brain tumours diagnosed during the first year of life. CPTs exhibit marked clinical and biological heterogeneity and are classified into three entities according to the World Health Organization (WHO): choroid plexus papilloma (CPP, WHO grade 1), atypical choroid plexus papilloma (aCPP, WHO grade 2) and choroid plexus carcinoma (CPC, WHO grade 3). Although CPP is a benign tumour with excellent prognosis following complete surgical resection, aCPP is defined by increased mitotic activity and carries a higher risk of recurrence in children older than 3 years and in adults. In addition, a subset of adult (a)CPPs harbours TERT promoter mutations, which have been associated with an increased risk of tumour recurrence. CPC is a highly malignant tumour characterised by frank signs of malignancy and aggressive clinical behaviour, with particularly poor outcomes in TP53-mutant cases, frequently associated with Li-Fraumeni syndrome. Accurate grading and distinction from histological mimics may be difficult, especially in small biopsy specimens or tumours with atypical features. In addition, the integration of molecular findings, including DNA methylation analysis and copy-number assessment, has become an important adjunct in the diagnostic evaluation of CPTs by improving diagnostic accuracy and providing additional prognostic information. In this review, we outline the histological and molecular characteristics of CPTs and highlight common diagnostic pitfalls and relevant differential diagnoses across different age groups.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70095"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basal Ganglia Lesion Associated With Faciobrachial Dystonic Seizures (FBDS) in Anti-LGI1 Encephalitis: A Clinicopathological Case Report.","authors":"Pinfei Ni, Haitao Ren, Siyuan Fan, Hongzhi Guan","doi":"10.1111/nan.70094","DOIUrl":"10.1111/nan.70094","url":null,"abstract":"<p><p>This case provides clinicopathological evidence supporting the association between FBDS and basal ganglia involvement in anti-LGI1 encephalitis. It highlights the diagnostic challenge posed by tumour-like unilateral basal ganglia lesions on MRI and underscores the importance of neuronal autoantibody testing before invasive procedures. In addition, this report contributes the first neuropathological description of basal ganglia involvement in anti-LGI1 encephalitis and summarises previously reported pathological findings.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70094"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Heterogeneity of TDP-43 Fragments in Alzheimer's Disease and Primary Age-Related Tauopathy by Artificial Intelligence (AI)-Based 3D Segmentation.","authors":"Gokhan Uruk, Rodolfo G Gatto, Nadia Hossain, Jennifer L Whitwell, R Ross Reichard, Keith A Josephs","doi":"10.1111/nan.70096","DOIUrl":"10.1111/nan.70096","url":null,"abstract":"<p><p>TAR DNA-binding protein 43 (TDP-43) inclusions are defining pathological features of frontotemporal lobar degeneration (FTLD) but are also often observed in Alzheimer's disease (AD) and primary age-related tauopathy (PART). TDP-43 in AD is either associated with cognitive impairment or a protective-life prolonging impact, and yet the localization, cellular and fragment characteristics of TDP-43 need to be determined. We investigated the relationships between TDP-43 volumetric inclusion burden in low likelihood AD (lAD) and definite PART by immunostaining against phosphorylated TDP-43 (pTDP-43), TDP-43 C terminal (TDP-C) and TDP-43 N-terminal (TDP-N) fragments combined with 3D confocal imaging taken from eight regions: amygdala (basolateral [amygdala-BL] and centromedial amygdala [amygdala-CM]), the hippocampus (Cornu Ammonis [CA]-1, CA2/3, CA4, dentate gyrus [DG] and subiculum [SUB]) and entorhinal cortex (ERC) and artificial intelligence (AI)-based segmentation via object recognition, reconstruction and quantification. We found amygdala-CM in lAD and PART to have the overall greatest burden of pTDP-43 whereas TDP-N burden in amygdala-BL of PART cases was greater than other TDP-43 fragments. There was no difference in TDP-43 burden in hippocampal subfields in PART. However, CA2/3 region showed greater pTDP-43 burden while TDP-N stood out in DG and SUB. Multiple comparisons among the groups revealed that TDP-C was the only fragment showing differences among PART and lAD in CA2/3, DG and SUB regions. Overall, unbiased AI-based volumetric burden analysis pipeline demonstrated unique fragment aggregation patterns in the neurodegenerative processes of PART and AD.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70096"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Significance of Cystatin C and Bunina Bodies in Amyotrophic Lateral Sclerosis Pathogenesis.","authors":"Sarah M Granger, Rosemary A Staniforth, Asbjorg Osk Snorradottir, Johnathan Cooper-Knock, Kurt J De Vos, J Robin Highley","doi":"10.1111/nan.70083","DOIUrl":"10.1111/nan.70083","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a fatal neurodegenerative disease primarily affecting motor neurons. Two key protein inclusions found in lower motor neurons serve as neuropathological hallmarks of the disease in human tissue: the TDP43-positive inclusion and the cystatin C-positive Bunina body. Despite their diagnostic specificity and presence in most sporadic and familial ALS cases, Bunina bodies remain poorly understood, and their true prevalence is likely underestimated. The co-occurrence of the Bunina body and the TDP43 inclusion may provide valuable insights into the development of TDP43 pathology in ALS. Thorough characterisation of the Bunina body is needed to understand this interplay and the broader pathomechanisms of disease. This review examines our current knowledge of Bunina bodies and the biochemical properties of cystatin C that may promote its aggregation. Sequestration and aggregation of cystatin C into Bunina bodies may diminish its neuroprotective functions, including cysteine protease inhibition, autophagy induction and anti-amyloidogenic activity, thereby contributing to ALS pathogenesis. This review also evaluates findings from human post-mortem tissue and ALS disease models, discussing the value and limitations of these models in the context of Bunina bodies and TDP43 pathology. Finally, we discuss cystatin C's use as a biomarker and its therapeutic potential. A deeper understanding of cystatin C biology, its relationship with TDP43 pathology and improved ALS models will be essential for determining whether targeting cystatin C could provide a viable avenue for future ALS therapies.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70083"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148352747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Methylation Profiling in IDH-Mutant Gliomas: Biological Evolution, Molecular Grading and Clinical Implementation.","authors":"Pietro Tralongo, Gabriele Ricciardi, Mariagiovanna Ballato, Vincenzo Fiorentino, Valeria Zuccalà, Giorgia Castellani, Quintino Giorgio D'Alessandris, Guido Fadda, Lucia Ricci-Vitiani, Maria Caffo, Maurizio Martini","doi":"10.1111/nan.70100","DOIUrl":"10.1111/nan.70100","url":null,"abstract":"<p><p>Mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) define a major subgroup of adult-type diffuse gliomas and induce accumulation of D-2-hydroxyglutarate, resulting in extensive DNA and histone methylation changes. This epigenetic reprogramming underlies the glioma CpG island methylator phenotype (G-CIMP) and contributes to tumour lineage, differentiation state and clinical behaviour. DNA methylation profiling has consequently evolved from a research tool into an important ancillary method for CNS tumour classification, molecular subclassification and copy-number analysis. This narrative review examines the biological basis, analytical platforms and clinical applications of DNA methylation profiling in IDH-mutant gliomas. Particular attention is given to the distinction between research-defined G-CIMP-high and G-CIMP-low states and classifier-defined lower-grade and high-grade methylation subclasses. High-grade signatures, including A_IDH_HG and G-CIMP-low, are associated with adverse genomic features and outcome but should not be considered interchangeable or used in isolation to assign CNS WHO grade. Their interpretation requires integration with histology and established molecular criteria, including homozygous CDKN2A/B deletion. The review also discusses array-based profiling, emerging Nanopore and long-read approaches, computational quality control, and the integration of methylation data with genomic and transcriptomic alterations. Longitudinal studies indicate that a subset of IDH-mutant astrocytomas undergoes methylation loss, copy-number accumulation and altered cell-state differentiation during progression, although these changes are not universal. The clinical relevance of MGMT promoter methylation is more context-dependent than in IDH-wildtype glioblastoma. Moreover, the INDIGO trial established the clinical activity of mutant IDH inhibition in selected Grade 2 gliomas but did not validate methylation class as a predictive biomarker or demonstrate complete epigenetic reversal. Emerging applications, including single-cell and spatial epigenomics, tumour microenvironment deconvolution and CSF methylation profiling, remain investigational. Overall, DNA methylation profiling is most valuable when used as integrated diagnostic and risk-stratification evidence within the complete histological, genomic and clinical context.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 4","pages":"e70100"},"PeriodicalIF":3.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13498940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Phenotypic Heterogeneity Within the Sporadic Creutzfeldt-Jakob Disease MV1 Subtype.","authors":"Satish K Nemani, Leonardo M Cortez, Jennifer Myskiw, Ignazio Cali, Stephanie A Booth, Gerard H Jansen, Valerie L Sim","doi":"10.1111/nan.70078","DOIUrl":"10.1111/nan.70078","url":null,"abstract":"<p><p>The MV1 subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is one of the least studied. Cases are defined by the presence of the methionine/valine (MV) polymorphism at codon 129 of the PRNP gene and a type 1 immunoblot pattern of pathological prion protein (PrP^D), where the unglycosylated PrP^D fragment migrates at ~21 kDa (T²¹). Because the originally described MV1 cases had T²¹ plus brain pathology indistinguishable from MM1 cases (small vacuoles), the MV1 subtype has historically been grouped with MM1. However, the recent identification of MV1 cases with immunoblot and pathological features similar to the VV1 subtype (T^21-20 doublet, larger vacuoles, ballooned neurons) has raised the possibility that the MV1 subtype is more heterogeneous than originally proposed. Here, we report three MV1 cases that further reveal the heterogeneity of this subtype. All cases were atypical in that they had persistent T²⁰ fragments, in isolation or combination with T²¹ or T¹⁹, when typed at pH 6.9, a finding that would have been missed if typing were undertaken at pH 8.0 only. Fragment proportions differed in different brain regions, and further examination found that the cases had mixed MM1/VV1 features, predominant VV1-like characteristics or features of the MV2C subtype. Two cases had small to intermediate-sized vacuoles and synaptic PrP staining. The third case had intermediate vacuolation, weak synaptic staining and coarse PrP deposits. We also describe, for the first time, the application of asymmetric-flow field-flow fractionation as a novel tool to discriminate sCJD subtypes based on size distributions of protease-resistant and protease-sensitive PrP^D. Overall, we propose that MV1 is a more heterogeneous subtype than previously appreciated, potentially existing along a spectrum from MM1-like to VV1-like phenotypes. Importantly, this biochemical heterogeneity may be underrepresented when subtyping is done at pH 8.0, so we recommend CJD subtyping be performed at pH 6.9 to avoid missing atypical or mixed cases.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 3","pages":"e70078"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VCING Scoring and White Matter Arteriolosclerosis Show Relationships to Dementia Status and White Matter Damage in an Unselected Ageing Brain Cohort.","authors":"S B Wharton, C D Richardson, B Ashford, H Brooke, S U Ahamed, D J Fillingham, J E Simpson, S Francis, C Brayne, F E Matthews","doi":"10.1111/nan.70081","DOIUrl":"10.1111/nan.70081","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular disease is associated with late-life dementia and other morbidities during life and commonly coexists with neurodegenerative pathologies. A complex variety of lesions can be documented, which has made development of standardised operationalised criteria difficult. A semiquantitative approach, vascular cognitive impairment neuropathology guidelines (VCING), has been developed that provides a score based on assessment of occipital white matter arteriolosclerosis, occipital leptomeningeal cerebral amyloid angiopathy (CAA) and the presence of any macroscopic infarct.</p><p><strong>Methods: </strong>We applied VCING assessment to an ageing population-derived neuropathology cohort derived from two subcentres of the cognitive function and ageing study (n = 158, 63.7% female and 36.3% male).</p><p><strong>Results: </strong>Vascular pathology using this method was common in this UK ageing population sample with 75% of individuals having a score of 1 or more. VCING score was associated with the presence of dementia at death, even accounting for Alzheimer's disease neuropathological change (ADNC). Of the VCING components, white matter arteriolosclerosis, but not CAA or infarcts, was associated with dementia (after adjustment for ADNC). VCING score was not associated with vascular risk factors during life, but males were at greater risk of a higher VCING score than females. VCING and arteriolosclerosis were associated with white matter pallor and perivascular space widening as markers of white matter damage. Venous collagenosis was also associated with white matter pallor. There was an association between VCING score and ADNC in regression analysis, and the association was particularly strong for the CAA component.</p><p><strong>Conclusions: </strong>VCING is a straightforward method to assess vascular pathology in neuropathology cohorts and retains its association with dementia. The arteriolosclerosis component, in particular, is related to dementia and to white matter damage, whereas venous-side effects may also be important for the latter. The strong association of the CAA component with ADNC measures, however, raises the question of whether the VCING approach may have some confounding effects with ADNC.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 3","pages":"e70081"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal White Matter Injury: Connecting Histology, Pathophysiology and Neurodevelopmental Outcomes.","authors":"Angela N Viaene","doi":"10.1111/nan.70084","DOIUrl":"10.1111/nan.70084","url":null,"abstract":"<p><p>The first descriptions of perinatal white matter injury and its proposed relationship to adverse neurological outcomes were published over 150 years ago. Initial studies highlighted the significance of prematurity in the development of this pathology. Although prematurity remains a significant risk factor in the development of perinatal white matter injury today, it can be seen in many clinical settings and is associated with hypoxic/ischaemic insults and inflammation. White matter injury is typically divided into the focal form, white matter necrosis (or periventricular leukomalacia) and the diffuse form, often referred to as diffuse white matter gliosis. Diffuse white matter gliosis is characterised by a proliferation of reactive astrocytes throughout the cerebral white matter and is associated with injury to pre-oligodendrocytes that results in the arrest of maturation and delayed myelination in surviving infants. White matter necrosis causes focal injury to the cellular components of the affected white matter as well as axons. However, axonal injury is also present in the diffuse form of white matter injury, even in the absence of necrosis, and the location of pre-oligodendrocytes correlates with sites of white matter injury, suggesting that the diffuse and focal forms of perinatal white matter injury may exist on a spectrum rather than as completely distinct entities. This review focuses on the macroscopic and microscopic features of white matter injury and how these relate to the proposed pathophysiology of this disease and adverse neurodevelopmental outcomes. Areas of uncertainty and future challenges are also discussed.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 3","pages":"e70084"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymptomatic Versus Symptomatic Alzheimer's Disease Neuropathology: A Systematic Review of Differences Reported in Post-Mortem Studies.","authors":"Thiago Guilherme Rêgo Barros, Laura Barbosa Grossi, Maria Letícia da Silva Campos, Israel Bem-Hur Netto Cardoso, Antônio Lúcio Teixeira, Aline Silva de Miranda, Eliana Cristina de Brito Toscano","doi":"10.1111/nan.70077","DOIUrl":"10.1111/nan.70077","url":null,"abstract":"<p><p>A subset of individuals exhibit substantial Alzheimer's disease (AD) neuropathology but remain asymptomatic (ASYMAD). The biological processes underlying this phenomenon remain poorly understood. We searched the PubMed/MEDLINE, Web of Science and CAPES databases to synthesise post-mortem brain tissue findings that differ between symptomatic and asymptomatic AD. Thirty-four studies met the predefined eligibility criteria. Multiple reports described lower levels of oligomeric Aβ and p-tau in ASYMAD, with reduced accumulation at synapses. Consistent with synaptic resilience, ASYMAD showed preserved expression of markers and proteomic signatures linked to synaptic function, homeostasis and plasticity. Further analyses supported preserved parenchymal architecture and dendritic and axonal morphology in ASYMAD. Some authors also described compensatory adaptations, including neuronal hypertrophy, increased neurogenesis and cellular antioxidant responses in ASYMAD brains. Additional findings indicated partial resistance to disruption of brain glucose, polyunsaturated fatty acid and one-carbon/polyamine metabolism. Glial and immune findings suggested a profile characterised by increased glial reactivity in specific regions and disease stages, alongside preserved glial homeostasis and lower cytokine expression in other contexts. In conclusion, although this review identified multiple processes potentially associated with the ASYMAD phenotype, the current evidence remains largely descriptive. Additionally, this synthesis is limited by substantial methodological heterogeneity and inconsistencies in data reporting. Future research should prioritise standardised clinicopathological definitions, pathology stage matching between ASYMAD and symptomatic AD groups, systematic assessment of mixed pathologies and further replication of exploratory findings to better elucidate the mechanisms underlying clinical resilience to AD neuropathology.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 3","pages":"e70077"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FTLD-TDP-43 With Motor Neuron Disease Pathology in an Autopsied Patient With Spastic Paraplegia-30B Harbouring a Homozygous KIF1A Variant.","authors":"Rie Saito, Arika Hasegawa, Tetsuya Takahashi, Ryoko Koike, Norikazu Hara, Ramil Gabdulkhaev, Kishin Koh, Akio Kawakami, Yoshihisa Takiyama, Takeshi Ikeuchi, Akiyoshi Kakita","doi":"10.1111/nan.70079","DOIUrl":"10.1111/nan.70079","url":null,"abstract":"<p><p>KIF1A-associated neurological disorder (KAND) is a rare hereditary condition caused by KIF1A variants, affecting axonal transport and presenting with a wide clinical spectrum, including hereditary spastic paraplegia. This case of childhood-onset KAND reveals FTLD-TDP43 with motor neuron disease pathology emerging late in the disease course, suggesting that HSP and FTLD-MND share a pathological continuum through a TDP-43-related pathway and expanding the clinicopathological spectrum of KAND.</p>","PeriodicalId":19151,"journal":{"name":"Neuropathology and Applied Neurobiology","volume":"52 3","pages":"e70079"},"PeriodicalIF":3.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}