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Acta Neuropathol 2022 May 25. Epub 2022 May 25.

Department of Clinical Immunology, Edouard Herriot University Hospital, 69003, Lyon, France.

Anti-synthetase syndrome (ASyS)-associated myositis is a major subgroup of the idiopathic inflammatory myopathies (IIM) and is characterized by disease chronicity with musculoskeletal, dermatological and pulmonary manifestations. One of eight autoantibodies against the aminoacyl-transferase RNA synthetases (ARS) is detectable in the serum of affected patients. However, disease-specific therapeutic approaches have not yet been established. Read More

Acta Neuropathol 2022 May 24. Epub 2022 May 24.

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.

Alzheimer's disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified FMNL2 (p = 6. Read More

Acta Neuropathol 2022 May 21. Epub 2022 May 21.

Department of Biology, University of Padova, Padua, Italy.

The Excitatory Amino Acid Transporter 2 (EAAT2) accounts for 80% of brain glutamate clearance and is mainly expressed in astrocytic perisynaptic processes. EAAT2 function is finely regulated by endocytic events, recycling to the plasma membrane and degradation. Noteworthy, deficits in EAAT2 have been associated with neuronal excitotoxicity and neurodegeneration. Read More

Acta Neuropathol 2022 May 20. Epub 2022 May 20.

Department of Brain and Neuroscience, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.

Acta Neuropathol 2022 May 19. Epub 2022 May 19.

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20814, USA.

Acta Neuropathol 2022 May 18. Epub 2022 May 18.

German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany.

Acta Neuropathol 2022 May 17. Epub 2022 May 17.

Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

Amyloid beta (Aβ) plaque is a defining pathologic feature of Alzheimer disease (AD). Aducanumab, a monoclonal IgG1 that selectively binds aggregated species of Aβ, has been shown by amyloid positron emission tomography (Amyloid PET) to reduce Aβ plaques in patients with prodromal and mild AD. This is the first autopsy report of the AD neuropathology in a patient previously treated with aducanumab. Read More

Acta Neuropathol 2022 May 17. Epub 2022 May 17.

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY, 10029, USA.

Traumatic brain injury (TBI) is a leading cause of neurologic impairment and death that remains poorly understood. Rodent models have yet to produce clinical therapies, and the exploration of larger and more diverse models remains relatively scarce. We investigated the potential for brain injury after headbutting in two combative bovid species by assessing neuromorphology and neuropathology through immunohistochemistry and stereological quantification. Read More

Acta Neuropathol 2022 May 14. Epub 2022 May 14.

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Acta Neuropathol 2022 May 12. Epub 2022 May 12.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, Box 29, Queen Square, London, WC1N 3BG, UK.

Mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures is associated with common variation at rs7587026, located in the promoter region of SCN1A. We sought to explore possible underlying mechanisms. SCN1A expression was analysed in hippocampal biopsy specimens of individuals with mesial temporal lobe epilepsy with hippocampal sclerosis who underwent surgical treatment, and hippocampal neuronal cell loss was quantitatively assessed using immunohistochemistry. Read More

Acta Neuropathol 2022 May 12. Epub 2022 May 12.

Department of Biostatics and Bioinformatics, Duke University Medical Center, Durham, USA.

Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is most often seen in the oldest-old (≥ 90 years of age) but can also be present in the younger-old (< 90 years of age). In this study, we compared the neuropathological associations of LATE-NC and contribution of LATE-NC to cognitive impairment between the oldest-old and younger-old. We observed significant differences in the prevalence of LATE-NC and its association with other co-pathologies in these two age groups. Read More

Acta Neuropathol 2022 May 10. Epub 2022 May 10.

Department of Neurology, Mayo Clinic, 200 1st St S.W., Rochester, MN, 55905, USA.

Acta Neuropathol 2022 Jun 6;143(6):713-731. Epub 2022 May 6.

Department of Paediatrics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.

Androgens and androgen-related molecules exert a plethora of functions across different tissues, mainly through binding to the transcription factor androgen receptor (AR). Despite widespread therapeutic use and misuse of androgens as potent anabolic agents, the molecular mechanisms of this effect on skeletal muscle are currently unknown. Muscle mass in adulthood is mainly regulated by the bone morphogenetic protein (BMP) axis of the transforming growth factor (TGF)-β pathway via recruitment of mothers against decapentaplegic homolog 4 (SMAD4) protein. Read More

Acta Neuropathol 2022 Jun 5;143(6):613-640. Epub 2022 May 5.

Department of Brain and Neuroscience, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.

Intracellular accumulation of abnormal proteins with conformational changes is the defining neuropathological feature of neurodegenerative diseases. The pathogenic proteins that accumulate in patients' brains adopt an amyloid-like fibrous structure and exhibit various ultrastructural features. The biochemical analysis of pathogenic proteins in sarkosyl-insoluble fractions extracted from patients' brains also shows disease-specific features. Read More

Acta Neuropathol 2022 Jun 30;143(6):697-711. Epub 2022 Apr 30.

Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT-TYR, ATRT-MYC and ATRT-SHH. ATRT-SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT-SHH might also have biological and clinical importance. Read More

Acta Neuropathol 2022 Jun 2;143(6):733-735. Epub 2022 May 2.

Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China.

Acta Neuropathol 2022 Jun 30;143(6):663-685. Epub 2022 Apr 30.

Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.

α-synuclein (αSyn) is an intrinsically disordered protein which can undergo structural transformations, resulting in the formation of stable, insoluble fibrils. αSyn amyloid-type nucleation can be induced by misfolded 'seeds' serving as a conformational template, tantamount to the prion-like mechanism. Accumulation of αSyn inclusions is a key feature of dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), and are found as additional pathology in Alzheimer's disease (AD) such as AD with amygdala predominant Lewy bodies (AD/ALB). Read More

Acta Neuropathol 2022 Jun 30;143(6):687-695. Epub 2022 Apr 30.

Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.

Frontotemporal lobar degeneration (FTLD) is a common cause of young onset dementia and is characterised by focal neuropathology. The reasons for the regional neuronal vulnerability are not known. Mitochondrial mechanisms have been implicated in the pathogenesis of FTLD, raising the possibility that frontotemporal regional mutations of mitochondrial DNA (mtDNA) are contributory causes. Read More

Acta Neuropathol 2022 Jun 26;143(6):641-662. Epub 2022 Apr 26.

Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.

Approximately half of Alzheimer's disease (AD) brains have concomitant Lewy pathology at autopsy, suggesting that α-synuclein (α-SYN) aggregation is a regulated event in the pathogenesis of AD. Genome-wide association studies revealed that the ε4 allele of the apolipoprotein E (APOE4) gene, the strongest genetic risk factor for AD, is also the most replicated genetic risk factor for Lewy body dementia (LBD), signifying an important role of APOE4 in both amyloid-β (Aβ) and α-SYN pathogenesis. How APOE4 modulates α-SYN aggregation in AD is unclear. Read More

Acta Neuropathol 2022 May 16;143(5):601-603. Epub 2022 Apr 16.

Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medical Center Göttingen (UMG), Georg-August-University, von-Siebold-Str. 5, 37075, Göttingen, Germany.

Acta Neuropathol 2022 May 12;143(5):571-583. Epub 2022 Apr 12.

Department of Neuroscience, Mayo Clinic-Florida, Jacksonville, FL, 32224, USA.

Tau deposition is one of two hallmark features of biologically defined Alzheimer's disease (AD) and is more closely related to cognitive decline than amyloidosis. Further, not all amyloid-positive individuals develop tauopathy, resulting in wide heterogeneity in clinical outcomes across the population with AD. We hypothesized that a polygenic risk score (PRS) based on tau PET (tau PRS) would capture the aggregate inherited susceptibility/resistance architecture influencing tau accumulation, beyond solely the measurement of amyloid-β burden. Read More

Acta Neuropathol 2022 May 11;143(5):605-607. Epub 2022 Apr 11.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Acta Neuropathol 2022 May 7;143(5):547-569. Epub 2022 Apr 7.

Department of Neuroscience, The Ohio State University, Columbus, OH, USA.

Selective neuronal vulnerability to protein aggregation is found in many neurodegenerative diseases including Alzheimer's disease (AD). Understanding the molecular origins of this selective vulnerability is, therefore, of fundamental importance. Tau protein aggregates have been found in Wolframin (WFS1)-expressing excitatory neurons in the entorhinal cortex, one of the earliest affected regions in AD. Read More

Acta Neuropathol 2022 May 2;143(5):531-545. Epub 2022 Apr 2.

Sanders-Brown Center On Aging, University of Kentucky, University of Kentucky, Lexington, KY, 40536, USA.

Transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) pathology is a hallmark of limbic-predominant age-related TDP-43 encephalopathy (LATE). The amygdala is affected early in the evolution of LATE neuropathologic change (LATE-NC), and heterogeneity of LATE-NC in amygdala has previously been observed. However, much remains to be learned about how LATE-NC originates and progresses in the brain. Read More

Acta Neuropathol 2022 May 31;143(5):609-612. Epub 2022 Mar 31.

Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.

Acta Neuropathol 2022 May 25;143(5):585-599. Epub 2022 Mar 25.

Comprehensive Epilepsy Center, Department of Neurology, NYU Langone Health and Grossman School of Medicine, New York, NY, USA.

Sudden unexplained death in childhood (SUDC) is death of a child over 1 year of age that is unexplained after review of clinical history, circumstances of death, and complete autopsy with ancillary testing. Multiple etiologies may cause SUDC. SUDC and sudden unexpected death in epilepsy (SUDEP) share clinical and pathological features, suggesting some similarities in mechanism of death and possible abnormalities in hippocampus and cortex. Read More

Acta Neuropathol 2022 04 22;143(4):419-425. Epub 2022 Mar 22.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.

Acta Neuropathol 2022 Apr 19;143(4):471-486. Epub 2022 Mar 19.

School of Psychology and Neuroscience, University of St Andrews, St Andrews, UK.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. Read More

Acta Neuropathol 2022 Apr 18;143(4):505-521. Epub 2022 Mar 18.

The Center for Neuroinflammation and Experimental Therapeutics and the Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Inhibition of Bruton's Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little is known; however, about how BTKi influences MS disease-implicated functions of B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, BTKi attenuates B-cell:T-cell interactions via a novel mechanism involving modulation of B-cell metabolic pathways which, in turn, mediates an anti-inflammatory modulation of the B cells. Read More

Acta Neuropathol 2022 04 7;143(4):527-529. Epub 2022 Mar 7.

ANSES-Laboratoire de Lyon (French Agency for Food, Environmental and Occupational Health & Safety), University of Lyon, 31 avenue Tony Garnier, 69364, Lyon, Cedex 7, France.