A novel temporal‐predominant neuro‐astroglial tauopathy associated with TMEM106B gene polymorphism in FTLD/ALS‐TDP
| العنوان: | A novel temporal‐predominant neuro‐astroglial tauopathy associated with TMEM106B gene polymorphism in FTLD/ALS‐TDP |
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| المؤلفون: | William W. Seeley, Gabor G. Kovacs, Eun-Joo Kim, Lorenzo Pasquini, Joel H. Kramer, Kevin Wojta, Salvatore Spina, Suzee E. Lee, Anna Karydas, Claudia K. Suemoto, Elisa de Paula França Resende, Jorge J. Llibre-Guerra, Bruce L. Miller, Isabel E. Allen, Shirley Yin-Yu Pang, Eliana Marisa Ramos, Ji Hye Hwang, Alexander J. Ehrenberg, Adam M. Staffaroni, Lea T. Grinberg |
| المصدر: | Brain Pathol |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Genotype, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, Article, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, C9orf72, mental disorders, medicine, Humans, Amyotrophic lateral sclerosis, Aged, Neurons, General Neuroscience, Amyotrophic Lateral Sclerosis, Neurodegeneration, Membrane Proteins, Frontotemporal lobar degeneration, Middle Aged, medicine.disease, 030104 developmental biology, Astrocytes, Frontotemporal Dementia, Female, Neurology (clinical), Tauopathy, Gene polymorphism, 030217 neurology & neurosurgery, Frontotemporal dementia |
| الوصف: | BACKGROUND: Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP-43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical, neuroglial tauopathy in cases harboring a TMEM106B rs1990622 A/A genotype. AIMS: To test whether TMEM106B genotype affects the risk of developing atypical tauopathy under a recessive genotype model (presence versus absence of two major alleles: A/A vs. A/G and G/G). METHODS: We characterized the atypical tauopathy neuropathologically and determined its frequency by TMEM106B rs1990622 genotypes in 90 postmortem cases with a primary diagnosis of FTLD/ALS-TDP [mean age at death 65.5 years (±8.1),40% female]. We investigated the effect of this new atypical tauopathy on demographics and clinical and neuropsychological metrics. We also genotyped TMEM106B in an independent series with phenotypically similar cases. RESULTS: Sixteen cases (16/90, 17.7 %) showed the temporal-predominant neuro-astroglial tauopathy, and 93.7% of them carried an A/A genotype (vs. ~35% in a population cohort). The odds ratio of FTLD/ALS-TDP individuals with the A/A genotype showing neuro-astroglial tauopathy was 13.9. Individuals with this tauopathy were older at onset (p=0.01). The validation cohort had a similarly high proportion of rs1990622 A/A genotype. TDP-43 and tau changes co-occur in a subset of neurons. CONCLUSIONS: Our data add to the growing body of evidence that TMEM106B polymorphisms may modulate neurodegeneration. A distinctive medial temporal predominant, 4-repeat, neuro-astroglial tauopathy strongly correlates to TMEM106B A/A genotype in FTLD/ALS-TDP cases. |
| تدمد: | 1750-3639 1015-6305 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a22478d31c0809a72a5a7b3dd7df5b8Test https://doi.org/10.1111/bpa.12924Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a22478d31c0809a72a5a7b3dd7df5b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17503639 10156305 |
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