Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease
| العنوان: | Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease |
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| المؤلفون: | Judith A. Steen, Dinorah Jean-Gilles, Pieter Beerepoot, Naomi Klickstein, Bradley T. Hyman, Mark B. De Los Santos, Tarun V. Kamath, Renee Moore, Arthur Viode, Aurélien Lathuilière, Lori B. Chibnik, Matthew P. Frosch, Ryan C. Clark, Derek H. Oakley, Alberto Serrano-Pozo, Benjamin D. Moore, Fiona Elwood, Rudolph E. Tanzi, Diana L. Corjuc, Simon Dujardin, Analiese R. Fernandes, Matthew E. Kennedy, Patrick M. Dooley, Bianca T. Corjuc, Kristina Mullin, Caitlin Commins, Kevin Atchison |
| المصدر: | Nat Med Nature medicine, Vol. 26, No 8 (2020) pp. 1256-1263 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cerebral Cortex / metabolism, Neurofibrillary Tangles / pathology, Disease, Protein aggregation, Severity of Illness Index, 0302 clinical medicine, Neurofibrillary Tangles / metabolism, Cognitive Dysfunction / pathology, Age of Onset, Phosphorylation, Aged, 80 and over, Cerebral Cortex, Tau Proteins / genetics, Cognition, Neurofibrillary Tangles, General Medicine, Middle Aged, Phenotype, 3. Good health, Alzheimer Disease / genetics, medicine.anatomical_structure, Cerebral Cortex / pathology, Cerebral cortex, 030220 oncology & carcinogenesis, Female, tau Proteins, Biology, Protein Aggregation, Pathological, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Genetic Heterogeneity, Alzheimer Disease, Protein Aggregation, Pathological / genetics, medicine, Humans, Cognitive Dysfunction, Aged, Protein Aggregation, Pathological / pathology, Genetic heterogeneity, Neurofibrillary Tangles / genetics, Alzheimer Disease / pathology, Cancer, medicine.disease, Alzheimer Disease / metabolism, 030104 developmental biology, Cognitive Dysfunction / genetics, Age of onset, Neuroscience |
| الوصف: | Alzheimer's disease (AD) causes unrelenting, progressive cognitive impairments, but its course is heterogeneous, with a broad range of rates of cognitive decline1. The spread of tau aggregates (neurofibrillary tangles) across the cerebral cortex parallels symptom severity2,3. We hypothesized that the kinetics of tau spread may vary if the properties of the propagating tau proteins vary across individuals. We carried out biochemical, biophysical, MS and both cell- and animal-based-bioactivity assays to characterize tau in 32 patients with AD. We found striking patient-to-patient heterogeneity in the hyperphosphorylated species of soluble, oligomeric, seed-competent tau. Tau seeding activity correlates with the aggressiveness of the clinical disease, and some post-translational modification (PTM) sites appear to be associated with both enhanced seeding activity and worse clinical outcomes, whereas others are not. These data suggest that different individuals with 'typical' AD may have distinct biochemical features of tau. These data are consistent with the possibility that individuals with AD, much like people with cancer, may have multiple molecular drivers of an otherwise common phenotype, and emphasize the potential for personalized therapeutic approaches for slowing clinical progression of AD. |
| تدمد: | 1546-170X 1078-8956 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc7bb689b9606b3271da239615caaeaaTest https://pubmed.ncbi.nlm.nih.gov/33514949Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bc7bb689b9606b3271da239615caaeaa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1546170X 10788956 |
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