Free neuropathology最新文献

{"title":"Neuromuscular disease: 2022 update.","authors":"Marta Margeta","doi":"10.17879/freeneuropathology-2022-3805","DOIUrl":"10.17879/freeneuropathology-2022-3805","url":null,"abstract":"<p><p>This review highlights ten important advances in the neuromuscular disease field that were reported in 2021. As with prior updates in this article series, the overarching topics include (i) advances in understanding of fundamental neuromuscular biology; (ii) new / emerging diseases; (iii) advances in understanding of disease etiology and pathogenesis; (iii) diagnostic advances; and (iv) therapeutic advances. Within this general framework, the individual disease entities that are discussed in more detail include neuromuscular complications of COVID-19 (another look at the topic first covered in the 2021 review), autosomal recessive myopathy caused by MLIP mutations, autosomal recessive neuromuscular disease caused by VWA1 mutations, Leber's hereditary optic neuropathy, myopathies with autophagic defects, tRNA synthetase-associated Charcot-Marie-Tooth disease, systemic sclerosis-associated myopathy, humoral immune endoneurial microvasculopathy, and late-onset Pompe disease. In addition, the review highlights a few other advances (including new insights into mechanisms of muscle and nerve regeneration and the use of gene expression profiling to better characterize different subtypes of immune-mediated myopathies) that will be of significant interest for clinicians and researchers who specialize in neuromuscular disease.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209905/pdf/freeneuropathol-03-05-3805.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9698940","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":"Neurooncology: 2022 update.","authors":"Pieter Wesseling, Jacob S Rozowsky","doi":"10.17879/freeneuropathology-2022-3804","DOIUrl":"10.17879/freeneuropathology-2022-3804","url":null,"abstract":"<p><p>This 'Neurooncology: 2022 update' presents topics that were selected by the authors as top ten discoveries published in 2021 in the broader field of neurooncological pathology. This time, the spectrum of topics includes: papers with a direct impact on daily diagnostic practice of CNS tumors in general and with information on how to improve grading of meningiomas; studies shedding new light on the oncogenesis of gliomas (in particular 'optic gliomas' and H3-mutant gliomas); several 'multi-omic' investigations unraveling the intra-tumoral heterogeneity of especially glioblastomas further; a study indicating the potential of 'repurposing' Prozac® for the treatment of glioblastomas; liquid biopsy using CSF for assessment of residual medulloblastoma. In the last part of this review some other papers are mentioned that didn't make it to this (quite subjective) top ten list.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2022-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209868/pdf/freeneuropathol-03-04-3804.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9963467","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":"Neuroinflammation: 2022 update.","authors":"Hans Lassmann","doi":"10.17879/freeneuropathology-2022-3790","DOIUrl":"10.17879/freeneuropathology-2022-3790","url":null,"abstract":"<p><p>Besides important progress in the understanding of the pathological substrate of COVID-19-associated brain disease, major insights into mechanisms of neurodegeneration in human disease have been provided in neuropathological studies published in 2021. Recently developed techniques, which allow the simultaneous detection of a large battery of different molecules within single cells, have proven useful in the analysis of disease mechanisms in experimental and human neuroinflammatory conditions. They have elucidated protective and detrimental effects of activated microglia, which act in a stage and context-dependent manner in the induction and propagation of neurodegeneration. In addition, they emphasize the importance of synaptic damage and of selective neuronal vulnerability in the respective diseases. The results provide important new insights with high clinical relevance.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2022-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209994/pdf/freeneuropathol-03-03-3790.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9591401","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":"Neuropathological findings in possible normal pressure hydro-cephalus: A post-mortem study of 29 cases with lifelines.","authors":"Joni J Hänninen, Madoka Nakajima, Aleksi Vanninen, Santtu Hytönen, Jaana Rummukainen, Anne Maria Koivisto, Juha E Jääskeläinen, Hilkka Soininen, Anna Sutela, Ritva Vanninen, Mikko Hiltunen, Ville Leinonen, Tuomas Rauramaa","doi":"10.17879/freeneuropathology-2022-3331","DOIUrl":"10.17879/freeneuropathology-2022-3331","url":null,"abstract":"<p><p><b>Aims:</b> There are very few detailed post-mortem studies on idiopathic normal-pressure hydrocephalus (iNPH) and there is a lack of proper neuropathological criteria for iNPH. This study aims to update the knowledge on the neuropathology of iNPH and to develop the neuropathological diagnostic criteria of iNPH. <b>Methods:</b> We evaluated the clinical lifelines and post-mortem findings of 29 patients with possible NPH. Pre-mortem cortical brain biopsies were taken from all patients during an intracranial pressure measurement or a cerebrospinal fluid (CSF) shunt surgery. <b>Results:</b> The mean age at the time of the biopsy was 70±8 SD years and 74±7 SD years at the time of death. At the time of death, 11/29 patients (38%) displayed normal cognition or mild cognitive impairment (MCI), 9/29 (31%) moderate dementia and 9/29 (31%) severe dementia. Two of the demented patients had only scarce neuropathological findings indicating a probable hydrocephalic origin for the dementia. Amyloid-β (Aβ) and hyperphosphorylated τ (HPτ) in the biopsies predicted the neurodegenerative diseases so that there were 4 Aβ positive/low Alzheimer's disease neuropathological change (ADNC) cases, 4 Aβ positive/intermediate ADNC cases, 1 Aβ positive case with both low ADNC and progressive supranuclear palsy (PSP), 1 HPτ/PSP and primary age-related tauopathy (PART) case, 1 Aβ/HPτ and low ADNC/synucleinopathy case and 1 case with Aβ/HPτ and high ADNC. The most common cause of death was due to cardiovascular diseases (10/29, 34%), followed by cerebrovascular diseases or subdural hematoma (SDH) (8/29, 28%). Three patients died of a postoperative intracerebral hematoma (ICH). Vascular lesions were common (19/29, 65%). <b>Conclusions:</b> We update the suggested neuropathological diagnostic criteria of iNPH, which emphasize the rigorous exclusion of all other known possible neuropathological causes of dementia. Despite the first 2 probable cases reported here, the issue of \"hydrocephalic dementia\" as an independent entity still requires further confirmation. Extensive sampling (with fresh frozen tissue including meninges) with age-matched neurologically healthy controls is highly encouraged.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10210004/pdf/freeneuropathol-03-02-3331.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9592666","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":"Soluble brain homogenates from diverse human and mouse sources preferentially seed diffuse Aβ plaque pathology when injected into newborn mouse hosts.","authors":"Brenda D Moore, Yona Levites, Guilian Xu, Hailey Hampton, Munir F Adamo, Cara L Croft, Hunter S Futch, Corey Moran, Susan Fromholt, Christopher Janus, Stefan Prokop, Dennis Dickson, Jada Lewis, Benoit I Giasson, Todd E Golde, David R Borchelt","doi":"10.17879/freeneuropathology-2022-3766","DOIUrl":"https://doi.org/10.17879/freeneuropathology-2022-3766","url":null,"abstract":"<p><strong>Background: </strong>Seeding of pathology related to Alzheimer's disease (AD) and Lewy body disease (LBD) by tissue homogenates or purified protein aggregates in various model systems has revealed prion-like properties of these disorders. Typically, these homogenates are injected into adult mice stereotaxically. Injection of brain lysates into newborn mice represents an alternative approach of delivering seeds that could direct the evolution of amyloid-β (Aβ) pathology co-mixed with either tau or α-synuclein (αSyn) pathology in susceptible mouse models.</p><p><strong>Methods: </strong>Homogenates of human pre-frontal cortex were injected into the lateral ventricles of newborn (P0) mice expressing a mutant humanized amyloid precursor protein (APP), human P301L tau, human wild type αSyn, or combinations thereof. The homogenates were prepared from AD and AD/LBD cases displaying variable degrees of Aβ pathology and co-existing tau and αSyn deposits. Behavioral assessments of APP transgenic mice injected with AD brain lysates were conducted. For comparison, homogenates of aged APP transgenic mice that preferentially exhibit diffuse or cored deposits were similarly injected into the brains of newborn APP mice.</p><p><strong>Results: </strong>We observed that lysates from the brains with AD (Aβ+, tau+), AD/LBD (Aβ+, tau+, αSyn+), or Pathological Aging (Aβ+, tau-, αSyn-) efficiently seeded diffuse Aβ deposits. Moderate seeding of cerebral amyloid angiopathy (CAA) was also observed. No animal of any genotype developed discernable tau or αSyn pathology. Performance in fear-conditioning cognitive tasks was not significantly altered in APP transgenic animals injected with AD brain lysates compared to nontransgenic controls. Homogenates prepared from aged APP transgenic mice with diffuse Aβ deposits induced similar deposits in APP host mice; whereas homogenates from APP mice with cored deposits induced similar cored deposits, albeit at a lower level.</p><p><strong>Conclusions: </strong>These findings are consistent with the idea that diffuse Aβ pathology, which is a common feature of human AD, AD/LBD, and PA brains, may arise from a distinct strain of misfolded Aβ that is highly transmissible to newborn transgenic APP mice. Seeding of tau or αSyn comorbidities was inefficient in the models we used, indicating that additional methodological refinement will be needed to efficiently seed AD or AD/LBD mixed pathologies by injecting newborn mice.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 9","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756325","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":"Medulloblastoma and Cowden syndrome: Further evidence of an association.","authors":"Steffen Albrecht, Barbara Miedzybrodzki, Laura Palma, Van Hung Nguyen, Roy W R Dudley, Torsten Pietsch, Tobias Goschzik, Nada Jabado, Catherine Goudie, William D Foulkes","doi":"10.17879/freeneuropathology-2022-3684","DOIUrl":"10.17879/freeneuropathology-2022-3684","url":null,"abstract":"<p><p>Cowden syndrome (CS) is an autosomal dominant hamartoma and tumor predisposition syndrome caused by heterozygous pathogenic germline variants in <i>PTEN</i> in most affected individuals. Major features include macrocrania, multiple facial tricholemmomas, acral and oral keratoses and papillomas, as well as mammary, non-medullary thyroid, renal, and endometrial carcinomas. Lhermitte-Duclos disease (LDD), or dysplastic gangliocytoma of the cerebellum, is the typical brain tumor associated with CS; the lifetime risk for LDD in CS patients has been estimated to be as high as 30%. In contrast, medulloblastoma is much rarer in CS, with only 4 reported cases in the literature. We report a 5th such patient. All 5 patients were diagnosed between 1 and 2 years of age and not all showed the pathognomonic clinical stigmata of CS at the time of their medulloblastoma diagnosis. Where detailed information was available, the medulloblastoma was of the SHH-subtype, in keeping with the observation that in sporadic medulloblastomas, <i>PTEN</i>-alterations are usually encountered in the SHH-subtype. Medulloblastomas can be associated with several tumor-predisposition syndromes and of the 4 medulloblastoma subtypes, SHH-medulloblastomas in children have the highest prevalence of predisposing germline variants (approx. 40%). CS should be added to the list of SHH-medulloblastoma-associated syndromes. Germline analysis of <i>PTEN</i> should be performed in infants with SHH-medulloblastomas, regardless of their clinical phenotype, especially if they do not carry pathogenic germline variants in <i>PTEN</i> or <i>PTEN</i>, the most commonly altered predisposing genes in this age-group. In addition, these cases show that CS has a biphasic brain tumor distribution, both in regards to the age of onset and the tumor type: a small number of CS patients develop a medulloblastoma in infancy while many more develop LDD in adulthood.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2022-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209873/pdf/freeneuropathol-03-01-3684.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9592665","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":"Cerebrovascular disease lesions are additive and tied to vascular risk factors and cognitive impairment.","authors":"John L Robinson, Hayley Richardson, Sharon X Xie, Brian Alfaro, Nicholas Loh, Virginia M-Y Lee, Edward B Lee, John Q Trojanowski","doi":"10.17879/freeneuropathology-2022-3792","DOIUrl":"10.17879/freeneuropathology-2022-3792","url":null,"abstract":"<p><p>Cerebrovascular lesions are prevalent in late life and frequently co-occur but the relationship to cognitive impairment is complicated by the lack of consensus around which lesions represent hallmark pathologies for vascular impairment, particularly in the presence of Alzheimer's disease (AD). We developed an easily applicable model of cerebrovascular disease (CVD), defined as the presence of two or more lesions: moderate to severe cerebral amyloid angiopathy, moderate to severe arteriolosclerosis, infarcts (large, lacunar, or micro), and/or hemorrhages. AD was defined as intermediate or high AD neuropathologic change. The contribution of vascular risk factors such as atherosclerosis and/or a health history of heart disease, hyperlipidemia, stroke events, diabetes, or hypertension was also assessed. Logistic regression analysis reported the association of CVD with increasing age, vascular risk factors, AD, and cognitive impairment in this study of 1,485 autopsied individuals. Cerebrovascular lesions were present in 48% and 16% had CVD. Increasing age associated with all lesions (p<0.001), except hemorrhages (p=0.41). CVD was more likely in individuals with vascular risk factors or AD (p<0.01). CVD, but not individual cerebrovascular lesions, associated with impairment in cases without AD (p<0.01), but not in cases with AD (p>0.61). From this, we conclude that a simple, additive model of CVD is 1) age and AD-associated, 2) is associated with vascular risk factors, and 3) clinically correlates with cognitive decline independent of AD.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209856/pdf/freeneuropathol-03-07-3792.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9552718","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":"Neuropathology Studies of Dementia in US Persons other than Non-Hispanic Whites.","authors":"My-le Nguyen, Emily Z Huie, Rachel A Whitmer, Kristen M George, Brittany N Dugger","doi":"10.17879/freeneuropathology-2022-3795","DOIUrl":"10.17879/freeneuropathology-2022-3795","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and vascular dementia are two of the most prevalent dementias that afflict the aging population in the United States (US). Studies have made great strides in understanding the neuropathology of these diseases; however, many studies are conducted in the context of non-Hispanic whites (NHWs), and few include the rapidly growing underrepresented populations that reside in the US. We sought to characterize current knowledge of the neuropathologic landscape of AD and vascular dementia of the largest growing US minority groups, namely Latinos/Hispanics, Black Americans, and Asian Americans, compared with NHWs being the majority group. It is vital to note these historic categories are social constructs and cultural and social associations may underlie differences.  We conducted a literature search utilizing specific criteria to yield neuropathology papers that addressed the demographics and neuropathologies of relevance, then collated the findings into this review. We reveal that while there has been much progress in neuropathological research involving Latinos/Hispanics and Black Americans in the past decade, no cohesive conclusions could be extrapolated from the existing data due to the dearth of minority participants and even smaller amount of information related to the heterogeneity within each minority group, especially Latinos/Hispanics. Furthermore, we reveal an even greater scarcity in neuropathological studies involving Asian Americans, also a very heterogeneous group. We hope the presented findings will illuminate the paucity of minority representation in not just neuropathological research but the field of clinical research overall and serve to inspire clinicians and researchers to help reduce the health disparities underrepresented groups in the US face.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"3 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580692","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":"Ex vivo MRI facilitates localization of cerebral microbleeds of different ages during neuropathology assessment.","authors":"Sukriti Nag, Er-Yun Chen, Ryan Johnson, Ashish Tamhane, Konstantinos Arfanakis, Julie A Schneider","doi":"10.17879/freeneuropathology-2021-3638","DOIUrl":"10.17879/freeneuropathology-2021-3638","url":null,"abstract":"<p><p>Cerebral microbleeds (CMBs) identified by in vivo magnetic resonance imaging (MRI) of brains of older persons may have clinical relevance due to their association with cognitive impairment and other adverse neurologic outcomes, but are often not detected in routine neuropathology evaluations. In this study, the utility of ex vivo MRI in the neuropathological identification, localization, and frequency of CMBs was investigated. The study included 3 community dwelling elders with Alzheimer's dementia, and mild to severe small vessel disease (SVD). Ex vivo MRI was performed on the fixed hemisphere to identify CMBs, blinded to the neuropathology diagnoses. The hemibrains were then sliced at 1 cm intervals and 2, 1 or 0 microhemorrhages (MH) were detected on the cut surfaces of brain slabs using the routine neuropathology protocol. Ex vivo imaging detected 15, 14 and 9 possible CMBs in cases 1, 2 and 3, respectively. To obtain histological confirmation of the CMBs detected by ex vivo MRI, the 1 cm brain slabs were dissected further and MHs or areas corresponding to the CMBs detected by ex vivo MRI were blocked and serially sectioned at 6 µm intervals. Macroscopic examination followed by microscopy post ex vivo MRI resulted in detection of 35 MHs and therefore, about 12 times as many MHs were detected compared to routine neuropathology assessment without ex vivo MRI. While microscopy identified previously unrecognized chronic MHs, it also showed that MHs were acute or subacute and therefore may represent perimortem events. Ex vivo MRI detected CMBs not otherwise identified on routine neuropathological examination of brains of older persons and histologic evaluation of the CMBs is necessary to determine the age and clinical relevance of each hemorrhage.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"2 ","pages":"35"},"PeriodicalIF":0.0,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209859/pdf/freeneuropathol-02-35-3638.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964074","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":"Friedreich cardiomyopathy is a desminopathy.","authors":"Arnulf H Koeppen, Rahman F Rafique, Joseph E Mazurkiewicz, Steven Pelech, Catherine Sutter, Qishan Lin, Jiang Qian","doi":"10.17879/freeneuropathology-2021-3679","DOIUrl":"10.17879/freeneuropathology-2021-3679","url":null,"abstract":"<p><p>Heart disease is an integral part of Friedreich ataxia (FA) and the most common cause of death in this autosomal recessive disease. The result of the mutation is lack of frataxin, a small mitochondrial protein. The clinical and pathological phenotypes of FA are complex, involving brain, spinal cord, dorsal root ganglia, sensory nerves, heart, and endocrine pancreas. The hypothesis is that frataxin deficiency causes downstream changes in the proteome of the affected tissues, including the heart. A proteomic analysis of heart proteins in FA cardiomyopathy by antibody microarray, Western blots, immunohistochemistry, and double-label laser scanning confocal immunofluorescence microscopy revealed upregulation of desmin and its chaperone protein, αB-crystallin. In normal hearts, these two proteins are co-localized at intercalated discs and Z discs. In FA, desmin and αB-crystallin aggregate, causing chaotic modification of intercalated discs, clustering of mitochondria, and destruction of the contractile apparatus of cardiomyocytes. Western blots of tissue lysates in FA cardiomyopathy reveal a truncated desmin isoprotein that migrates at a lower molecular weight range than wild type desmin. While desmin and αB-crystallin are not mutated in FA, the accumulation of these proteins in FA hearts allows the conclusion that FA cardiomyopathy is a desminopathy akin to desmin myopathy of skeletal muscle.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"2 ","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209862/pdf/freeneuropathol-02-34-3679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9583612","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}