Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)
Опубликована: Май 30, 2025
Язык: Английский
Behavioural Brain Research, Год журнала: 2025, Номер 484, С. 115524 - 115524
Опубликована: Март 4, 2025
Язык: Английский
Процитировано
3
Alzheimer s & Dementia, Год журнала: 2025, Номер 21(2)
Опубликована: Фев. 1, 2025
Abstract Hippocampal atrophy on magnetic resonance imaging is an important biomarker in Alzheimer's disease (AD). While hippocampal was thought to result from tau tangles AD, different neuropathologies can lead atrophy, especially TAR DNA‐binding protein 43 (TDP‐43) pathology. In this narrative review, we evaluate existing studies the relative contribution of and TDP‐43 pathology medial temporal lobe (MTL) atrophy. We report a clear association both neuropathology with MTL even after correcting for other neuropathologies. Next, discuss potential synergism between timing effects Finally, avenues future research will be discussed. A better understanding interplay their effect help development more specific biomarkers limbic‐predominant age‐related encephalopathy pinpointing optimal testing anti‐tau anti‐TDP‐43 treatments trials. Highlights Both contribute There positive potentially synergism. It unclear if have additive or synergistic The remains unclear. Clarifying improve biomarkers.
Язык: Английский
Процитировано
1
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 14, 2025
Tau exhibits change in both spatial extent and density of pathology along the Alzheimer's disease (AD) spectrum with each aspect contributing to overall burden pathological tau. Nevertheless, studies using PET have measured either magnitude standardized uptake value ratios (SUVRs) or number Tau+ regions. We hypothesized that combining these two dimensions into a single measure Magnitude eXtent, Tau-MaX, would provide improved quantification global tau as well allowing for region-agnostic does not require pre-specified region interest (ROI) meta-ROI. To test this hypothesis, we analyzed 18 F-flortaucipir scans from local national consortium data (n=1077 participants total) used Gaussian-mixture models 64 brain regions, define positivity magnitude. examined cross-sectional longitudinal Tau-MaX across compared association magnitude, plasma p-tau 217 cognition. also global, approach temporal lobe Braak stage meta-ROIs. Whereas separate assessments found earlier increases later was able dynamically capture shift demonstrating stronger preclinical clinical stages. Global differed between stages cross-sectionally changed over time all disease. Further, significantly associations cognition alone. Finally, measures performed similarly meta-ROI Tau-MaX. Together, findings indicate provides robust changes throughout course is associated blood-based biomarkers This may be particular use staging, serving an outcome monitor response therapeutic intervention.
Язык: Английский
Процитировано
0
Neurology International, Год журнала: 2025, Номер 17(5), С. 75 - 75
Опубликована: Май 13, 2025
Tau protein plays a pivotal role in maintaining neuronal structure and function through its regulation of microtubule stability polarity. Encoded by the MAPT gene, exists multiple isoforms due to alternative mRNA splicing, with differential expression central peripheral nervous systems. In healthy neurons, tau is selectively localized translated axons, process tightly regulated untranslated regions (UTRs) RNA-binding proteins such as HuD FMRP. Pathologically, undergoes hyperphosphorylation, misfolding, aggregation, which contribute neurodegeneration range disorders collectively known tauopathies. Alzheimer's disease (AD) most prevalent tauopathy, where abnormal accumulation temporal frontal lobes correlates cognitive decline behavioral symptoms. Other tauopathies, including Progressive Supranuclear Palsy (PSP), Corticobasal Degeneration (CBD), Frontotemporal Dementia Parkinsonism (FTDP-17), Pick's disease, are distinguished predominance specific (3R or 4R), cellular distribution, affected brain regions. Notably, astroglial tauopathies highlight pathological glial cells, expanding understanding beyond neurons. Despite advances imaging biomarkers (e.g., Tau-PET) molecular diagnostics, effective disease-modifying therapies for remain elusive. Ongoing research targets immunotherapies, splicing modulators, kinase inhibitors, antisense oligonucleotides, aiming mitigate pathology deleterious effects. Understanding multifaceted roles contexts critical developing future therapeutic strategies against
Язык: Английский
Процитировано
0
Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)
Опубликована: Май 28, 2025
Postmortem neuropathological examination, while the gold standard for diagnosing neurodegenerative diseases, often relies on limited regional sampling that may miss critical areas affected by Alzheimer's disease and related disorders. Ultra-high resolution postmortem MRI can help identify regions fall outside diagnostic criteria additional histopathologic evaluation. However, there are no standardized guidelines integrating histology in a traditional brain bank. We developed comprehensive protocol whole hemisphere 7T MRI-guided histopathological with whole-slide digital imaging analysis, providing reliable pipeline high-volume banking heterogeneous tissue. Our method uses patient-specific 3D printed molds built from MRI, allowing tissue processing permanent spatial reference frame. To facilitate pathology-MRI association studies, we created semi-automated to registration quantitative pathology scoring system using weakly supervised deep learning. validated this cohort of 29 brains diagnosis AD spectrum revealed correlations between cortical thickness phosphorylated tau accumulation. This has broad applicability across research banking, facilitating large-scale studies integrate neuroimaging. The innovations presented here provide scalable reproducible approach studying pathology, implications advancing therapeutic strategies
Язык: Английский
Процитировано
0
Alzheimer s Research & Therapy, Год журнала: 2025, Номер 17(1)
Опубликована: Май 30, 2025
Язык: Английский
Процитировано
0