The Role of Tau in Neuronal Function and Neurodegeneration DOI Creative Commons
Gonzálo Emiliano Aranda-Abreu, Fausto Rojas-Durán, Marı́a Elena Hernández

et al.

Neurology International, Journal Year: 2025, Volume and Issue: 17(5), P. 75 - 75

Published: May 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

Language: Английский

Role of tau versus TDP‐43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease DOI Creative Commons
Laura Wisse, Anika Wuestefeld,

Melissa Murray

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 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.

Language: Английский

Citations

1
Tau Burden is Best Captured by Magnitude and Extent: Tau-MaX as a Measure of Global Tau DOI Creative Commons
Christopher Brown, Sandhitsu R. Das, Katheryn A Q Cousins

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

0
Role of RhoA-ROCK signaling inhibitor fasudil in Alzheimer disease DOI
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed

et al.

Behavioural Brain Research, Journal Year: 2025, Volume and Issue: 484, P. 115524 - 115524

Published: March 4, 2025

Language: Английский

Citations

0
The Role of Tau in Neuronal Function and Neurodegeneration DOI Creative Commons
Gonzálo Emiliano Aranda-Abreu, Fausto Rojas-Durán, Marı́a Elena Hernández

et al.

Neurology International, Journal Year: 2025, Volume and Issue: 17(5), P. 75 - 75

Published: May 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

Language: Английский

Citations

0