Neuronal Tau Pathology Worsens Late Phase White Matter Degeneration After Traumatic Brain Injury in Transgenic Mice DOI Creative Commons
Fengshan Yu, Diego Iacono, Daniel P. Perl

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 30, 2023

ABSTRACT Traumatic brain injury (TBI) causes diffuse axonal which can produce chronic white matter pathology and subsequent post-traumatic neurodegeneration with poor patient outcomes. Tau modulates axon cytoskeletal functions undergoes phosphorylation mis-localization in neurodegenerative disorders. The effects of tau on after TBI are unclear. We used mice neuronal expression human mutant to examine pathological TBI. Adult male female hTau.P301S (Tg2541) transgenic wild type (Wt) received either moderate single (s-TBI) or repetitive mild (r-mTBI; once daily x 5), matched sham procedures. Acutely, s-TBI produced more extensive damage the corpus callosum (CC) as compared r-mTBI. After s-TBI, significant CC thinning was present at 6 weeks 4 months post-injury Wt mice, homozygous producing additional late demyelination. In contrast, r-mTBI did not except time point exhibited atrophy (−29.7%) increased microgliosis, but astrogliosis. Serum biomarker quantification demonstrated neurofilament light detection early one day mice. At months, high implicated pathology. Conclusions: Neuronal differentially exacerbated based severity chronicity. Ongoing from became accompanied by Pathological significantly worsened during phase

Language: Английский

Recent Advances in Targeting Transition Metals (Copper, Iron, and Zinc) in Alzheimer’s Disease DOI

Raghuraj Singh,

Archna Panghal,

Krishna Jadhav

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(12), P. 10916 - 10940

Published: May 29, 2024

Language: Английский

Citations

12
Testing the structural disconnection hypothesis: Myelin content correlates with memory in healthy aging DOI Creative Commons

Andrea Mendez Colmenares,

Michael L. Thomas,

Charles B. Anderson

et al.

Neurobiology of Aging, Journal Year: 2024, Volume and Issue: 141, P. 21 - 33

Published: May 23, 2024

The "structural disconnection" hypothesis of cognitive aging suggests that deterioration white matter (WM), especially myelin, results in decline, yet vivo evidence is inconclusive. We examined age differences WM microstructure using Myelin Water Imaging and Diffusion Tensor 141 healthy participants (age 20-79). used the Virginia Cognitive Aging Project NIH Toolbox® to generate composites for memory, processing speed, executive function. Voxel-wise analyses showed lower myelin water fraction (MWF), predominantly prefrontal WM, genu corpus callosum, posterior limb internal capsule was associated with reduced memory performance after controlling age, sex, education. In structural equation modeling, MWF callosum significantly mediated effect on whereas fractional anisotropy (FA) did not. Our findings support disconnection hypothesis, showing decline contributes age-related loss opens avenues interventions targeting health.

Language: Английский

Citations

5
Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non‐demented individuals DOI Creative Commons
Luigi Lorenzini,

Lyduine E. Collij,

Niccolo Tesí

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6146 - 6160

Published: July 29, 2024

Abstract INTRODUCTION Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, a key step toward precision medicine. METHODS We computed pathway‐specific scores (GRSs) in non‐demented individuals investigated AD variants predict cerebrospinal fluid (CSF) imaging biomarkers reflecting pathology, cardiovascular, white matter integrity, brain connectivity. RESULTS CSF amyloidbeta phosphorylated tau were most GRSs. Inflammatory pathways associated with cerebrovascular disease, whereas quantitative measures of lesion microstructure integrity predicted by clearance migration pathways. Functional connectivity alterations involved signal transduction synaptic communication. DISCUSSION This study reveals distinct profiles association pathophysiological aspects predementia stages AD, unraveling the substrates heterogeneity AD‐associated endophenotypes promoting forward understanding development personalized therapies. Highlights Polygenic for encompasses six that can be quantified scores, differentially relate biomarkers. are mostly burden. White health membrane functional communication

Language: Английский

Citations

5
Design, Synthesis, and Biological Evaluation of Imidazolylacetophenone Oxime Derivatives as Novel Brain-Penetrant Agents for Alzheimer’s Disease Treatment DOI

Zhao-Yuan Bian,

Peng‐Xiao Li,

Xu-Yao Feng

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 278, P. 116794 - 116794

Published: Aug. 30, 2024

Language: Английский

Citations

4
Relation of Alzheimer's disease-related TDP-43 proteinopathy to metrics from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). DOI Creative Commons
Anna Lavrova,

Nha Trang Thu Pham,

Robert I. Reid

et al.

Neurobiology of Aging, Journal Year: 2025, Volume and Issue: 150, P. 97 - 108

Published: March 8, 2025

Transactive response DNA-binding protein 43 kDa (TDP-43) deposition is linked to regional brain atrophy in Alzheimer's disease (AD), but diffusion changes associated with AD-related TDP-43 proteinopathy remain underexplored. This study evaluates the potential of tensor imaging (DTI) and neurite orientation dispersion density (NODDI) as vivo markers for detecting AD. We analyzed DTI NODDI metrics 49 cases AD neuropathologic changes, categorized by postmortem status. Diffusion from temporal lobe gray white matter regions key tracts were compared between TDP-43-positive negative cases. Group differences significant left hippocampus, amygdala, uncinate fasciculus after adjusting age, Braak neurofibrillary tangle (NFT) stage APOE ε4 showed increased mean diffusivity (MD) altered index (NDI) (ODI). Area under receiver operating characteristic curve (AUROC) analysis revealed high predictive accuracy amygdala ODI (AUC = 0.809, sensitivity 0.81, specificity 0.76), hippocampal MD 0.763, 0.67), 0.782, 0.88, 0.61). Combined, DTI/NODDI predictors demonstrated stronger discriminative ability 0.856, 0.76). These findings suggest that specific lobe. metrics, particularly MD, NDI, ODI, may improve antemortem detection pathology

Language: Английский

Citations

0
Visualize neuronal membrane cholesterol with split- fluorescent protein tagged YDQA sensor DOI Creative Commons
Yi Xu,

S Li,

Yiran Xu

et al.

Journal of Lipid Research, Journal Year: 2025, Volume and Issue: unknown, P. 100781 - 100781

Published: March 1, 2025

Language: Английский

Citations

0
Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice DOI Creative Commons
Fengshan Yu, Diego Iacono, Daniel P. Perl

et al.

Acta Neuropathologica, Journal Year: 2023, Volume and Issue: 146(4), P. 585 - 610

Published: Aug. 14, 2023

Traumatic brain injury (TBI) causes diffuse axonal which can produce chronic white matter pathology and subsequent post-traumatic neurodegeneration with poor patient outcomes. Tau modulates axon cytoskeletal functions undergoes phosphorylation mis-localization in neurodegenerative disorders. The effects of tau on after TBI are unclear. We used mice neuronal expression human mutant to examine pathological TBI. Adult male female hTau.P301S (Tg2541) transgenic wild-type (Wt) received either moderate single (s-TBI) or repetitive mild (r-mTBI; once daily × 5), sham procedures. Acutely, s-TBI produced more extensive damage the corpus callosum (CC) as compared r-mTBI. After s-TBI, significant CC thinning was present at 6 weeks 4 months post-injury Wt mice, homozygous producing additional late demyelination. In contrast, r-mTBI did not except time point exhibited atrophy (- 29.7%) increased microgliosis. Serum neurofilament light quantification detected traumatic 1 day post-TBI mice. At months, high implicated pathology. These findings have sex differences detected. Conclusions: Neuronal differentially exacerbated based severity chronicity. Ongoing from became accompanied by Pathological significantly worsened during phase

Language: Английский

Citations

9
Aerobic Exercise Facilitates the Nuclear Translocation of SREBP2 by Activating AKT/SEC24D to Contribute Cholesterol Homeostasis for Improving Cognition in APP/PS1 Mice DOI Open Access
Zelin Hu,

Yang-Qi Yuan,

Zhen Tong

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12847 - 12847

Published: Aug. 16, 2023

Impaired cholesterol synthesizing ability is considered a risk factor for the development of Alzheimer's disease (AD), as evidenced by reduced levels key proteases in brain that mediate synthesis; however, deposition has been found neurons tangles brains AD patients. Although it shown statins, which inhibit synthesis, reduce incidence AD, this seems paradoxical patients whose capacity already impaired. In study, we aimed to investigate effects aerobic exercise on metabolism APP/PS1 mice and reveal mechanisms improves cognitive function mice. Our study demonstrates reduction SEC24D protein, component coat protein complex II (COPII), synthesis 12 weeks was able promote recovery through activation kinase B (AKT), turn promoted expression mem-brane-bound sterol regulatory element-binding 2 (SREBP2) nuclear translocation mediating synthesis. Simultaneous restored transport with efflux excess from neuronal lipid rafts, thereby reducing cleavage APP amyloid pathway. emphasizes potential restoring intracerebral homeostasis therapeutic strategy alleviate impairment

Language: Английский

Citations

8
Reduced rapid eye movement sleep in late middle-aged and older apolipoprotein E ɛ4 allele carriers DOI Creative Commons
Claire André, Marie‐Ève Martineau‐Dussault, Andrée‐Ann Baril

et al.

SLEEP, Journal Year: 2024, Volume and Issue: 47(7)

Published: April 18, 2024

Abstract Study Objectives Apolipoprotein E ɛ4 (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). In addition, APOE4 carriers may exhibit sleep disturbances, but conflicting results have been reported, such that there no clear consensus regarding which aspects of are impacted. Our objective was to compare architecture between and non-carriers, investigate modulating impact age, sex, cognitive status, obstructive apnea (OSA). Methods A total 198 dementia-free participants aged >55 years old (mean age: 68.7 ± 8.08 old, 40.91% women, 41 carriers) were recruited in this cross-sectional study. They underwent polysomnography, genotyping, a neuropsychological evaluation. ANCOVAs assessed effect status on architecture, controlling apnea–hypopnea index. Interaction terms added covariates. Results Rapid eye movement (REM) percentage (F = 9.95, p .002, ηp2 0.049) duration 9.23, .003, 0.047) lower carriers. The replicated subsample 112 without moderate-to-severe OSA. There significant interactions OSA whole sample. Conclusions show REM duration, including cognitively unimpaired individuals, possibly resulting from early neurodegenerative processes regions involved generation maintenance.

Language: Английский

Citations

2
The relationship between acrylamide and neurodegenerative diseases: gut microbiota as a new intermediate cue DOI
Xinrui Xu, Siyu Wei,

Mengyi Lin

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: Dec. 13, 2024

Acrylamide (AA), a compound formed during the thermal processing of high-carbohydrate foods, has been implicated in onset and progression neurodegenerative diseases. An increasing number reports support that gut microbiota plays significant role brain function diseases, suggesting it may act as mediator between AA exposure development Available studies have shown intake affects composition integrity intestinal barrier, both which are often thought to be associated with pathogenesis given numerous evidences linking brain. Based on current understanding, this paper discusses induces diseases by disrupting structure barrier. Furthermore, explores interaction probiotics exposure, well potential for polysaccharides polyphenols improve microenvironment, provides novel perspectives modulating caused through diet.

Language: Английский

Citations

2