The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders DOI Creative Commons
Alessandro Galgani,

Marco Scotto,

Filippo Sean Giorgi

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(9), P. 10180 - 10199

Published: Sept. 14, 2024

Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that markedly precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson’s Alzheimer’s diseases. In humans, although tools have been developed to infer information on these nuclei, encompassing neuroimaging neurophysiological methods, a detailed specific direct evaluation their cellular features vivo has difficult obtain until recent years. The development induced pluripotent stem cell (iPSC) models allowed research deeply delve into molecular biology NSS neurons. fact, iPSCs can be produced easily non-invasively from patients’ fibroblasts or circulating blood monocytes, by de-differentiating those cells using protocols, then re-differentiated towards neural phenotypes, which may reproduce correspondent brain neurons (including ones) same patient. this review, we summarized findings obtained field NDDs iPSCs, with aim understand how reliably might represent vitro NSS. We found most current literature NSSs focused midbrain dopaminergic disease, providing interesting results pathophysiology even leading first human autologous transplantation. Differentiation protocols for noradrenergic, cholinergic, serotoninergic also recently defined published. Thus, it expected near future, approach could extend other NDDs.

Language: Английский

Ageing-Related Neurodegeneration and Cognitive Decline DOI Open Access
Irina Alafuzoff, Sylwia Libard

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 4065 - 4065

Published: April 5, 2024

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to morgue Uppsala University Hospital during a 15-year-long period. Among 1610 were ≥41 years age (range 41 102 years). Overall, hyperphosphorylated (HP) τ observed in brains 98% and amyloid β-protein (Aβ) 64%. The most common alteration Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) 26% subjects. In 16% HPτ limited locus coeruleus. 14 subjects (<1%), no altered proteins observed. 3 only Aβ observed, 17, distribution other than seen ADNC/PART. transactive DNA-binding protein 43 (TDP43) associated with limbic-predominant TDP encephalopathy (LATE) 565 (35%) α-synuclein (αS) pathology, i.e., Lewy body (LBD) or multi system atrophy (MSA) 21% A total 39% ADNC, 59% PART, 81% coeruleus lacked concomitant pathologies, LATE-NC LBD-NC. Of 293 (18% subjects) dementia, exhibited high intermediate level ADNC. 84% individuals various degrees alterations observed; MIXED-NC cause dementia. PART 10 dementia (3%), tangle-predominant No vascular NC (VNC), but 17 severe VNC might have contributed cognitive decline. Age-related tau astrogliopathy (ARTAG) 37% 53% those

Language: Английский

Citations

6
The effects of transcranial direct current stimulation on global cognition in patients with Alzheimer's disease: An update meta-analysis DOI Creative Commons
Siyuan Su, Ruihan Huang, Y Liu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Background Alzheimer's disease (AD) is a neurodegenerative disease. At present, there are currently no drugs that can cure AD. Objective A number of empirical studies have shown transcranial direct current stimulation (tDCS) may be used to treat cognitive abnormalities in patients with We will through meta-analysis reviews tDCS overall research on the effects function Methods Systematic searches were performed PubMed, Embase, and Cochrane Library databases from their creation until 8 March 2024. Using fixed effect model random evaluate average difference between treatment group control (MD) its 95% confidence interval (CI). Results The study included 10 randomized controlled trials (Nactive = 165, Nsham 167). results analysis showed did not significantly improve (SMD 0.17; 95%CI −0.05, 0.39; p 0.14; I² 51%). Quality life AD after was also evaluated, but improvement seen. Subgroup significant global treatment. sensitivity confirm reliability data, risk assessment find any high-risk projects. Conclusions Further future help explore new schemes for patients.

Language: Английский

Citations

0
Playful brains: a possible neurobiological pathway to cognitive health in aging DOI Creative Commons
Yulia Golland, Boaz M. Ben‐David, Mara Mather

et al.

Frontiers in Human Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 7, 2025

Healthy cognitive aging emphasizes preserving functions essential for independence and well-being. Developing interventions that promote cognition resilience in older individuals is crucial. Social playfulness, characterized by spontaneity mutual enjoyment, allows to step away from routine roles engage novel surprising exchanges. Emerging evidence suggests social playfulness a promising approach supporting joyful engaging way. In this theory hypothesis manuscript, we propose neurobiological pathway mediating the effects of on cognition. Playful interactions generate high levels uncertainty, requiring continuous adaptation exploration. We suggest these demands locus coeruleus-noradrenaline (LC-NA) system, which crucial navigating uncertainty sustaining arousal flexibility needed adapt dynamic unpredictable nature playful interactions. Importantly, collaborative safe environment transforms uncertainty-driven noradrenergic activation into an rewarding experience, enhancing focus, positive affect, flexibility. adults, where LC-NA functionality may decline with age, could counteract upregulating system. review linking integrity health explore how might mitigate deterioration functioning training executive promoting novelty This framework bridges neuroscience, psychology, creative-arts therapies, highlighting as tool healthy aging. emphasize need further research validate its implications designing leverage enhance populations.

Language: Английский

Citations

0
Fading Blue: Exploring the Causes of Locus Coeruleus Damage Across the Lifespan DOI Creative Commons
Alessandro Galgani,

Marco Scotto,

Ugo Faraguna

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 255 - 255

Published: Feb. 22, 2025

Locus Coeruleus (LC) is a brain nucleus that involved in variety of key functions (ranging from attention modulation to sleep-wake cycle regulation, memory encoding); its proper function necessary both during development and for integrity maintenance, at the microscale macroscale level. Due their specific intrinsic extrinsic features, LC cells are considered particularly susceptible damage concerning insults. This explains involvement degenerative diseases not only adults (in context neurodegenerative disease, mainly), but also children relation early hypoxic Down's Syndrome, among others). In this narrative review, we dissect potential mechanisms through which affected different diseases, with special emphasis on high rate activity it subjected oxidative stress associated it. Further research aimed deepening our understanding these needed enable strategies future could slow down degeneration subjects predisposed disorders.

Language: Английский

Citations

0
Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer’s disease, suspected-LATE and frontotemporal dementia DOI Creative Commons
Julien Lagarde, Pauline Olivieri, Mattéo Tonietto

et al.

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 3, 2024

Abstract Background The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages Alzheimer’s disease (AD). Little is known about LC NBM alteration limbic-predominant age-related TDP-43 encephalopathy (LATE) frontotemporal dementia (FTD). aim present study to investigate vivo integrity patients with suspected-LATE, early-amnestic AD FTD comparison controls. Methods Seventy-two participants (23 amnestic-AD patients, 17 defined by a clinical-biological diagnosis reinforced amyloid tau PET imaging, 15 controls) underwent neuropsychological assessment 3T brain MRI. We analyzed signal intensity (LC-I) volume as well their relation cognition medial temporal/cortical atrophy. Results found significantly lower LC-I suspected-LATE In FTD, we also observed but slightly less marked LC-I, independently temporal or frontal phenotype. was correlated global cognitive efficiency patients. Strong correlations were between that structures, particularly amygdala both Conclusions amnestic-AD, presumed-LATE suggests common vulnerability these structures different proteinopathies. Targeting noradrenergic cholinergic systems could be effective therapeutic strategies LATE FTD.

Language: Английский

Citations

3
Fully Automated MRI-based Analysis of the Locus Coeruleus in Aging and Alzheimer’s Disease Dementia using ELSI-Net DOI Creative Commons
Max Dünnwald,

Friedrich Krohn,

Alessandro Sciarra

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Abstract INTRODUCTION The Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimer’s Disease (AD). Magnetic Resonance Imaging based LC features have shown potential assess integrity in vivo. METHODS We present a Deep Learning segmentation feature extraction method: ELSI-Net apply it healthy aging AD dementia datasets. Agreement expert raters previously published atlases were assessed. aimed reproduce reported differences correlate extracted cerebrospinal fluid (CSF) biomarkers pathology. RESULTS demonstrated high agreement atlases. Previously group detected correlations CSF found. DISCUSSION Although we found excellent performance, further evaluations on more diverse datasets from clinical cohorts are required for conclusive assessment ELSI-Nets general applicability. Highlights thorough evaluation fully automatic method termed outperforms previous work shows with manual ratings replicates ELSI-Net’s volume correlates pathology RESEARCH IN CONTEXT Systematic Review: authors reviewed literature using traditional sources (e.g. Pubmed, Google Scholar). there several publications introducing semi-automatic methods segmentation, application underexplored. To best our knowledge, this first paper approach automated dementia. Interpretation: Our introduces evaluates an improved automatic, analysis approach. results suggest very practical applicability, e.g. large-scale studies diseases. Future Directions: can be used large- or small-scale ensure robust should evaluated larger, comprising varying MRI protocols populations.

Language: Английский

Citations

1
The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders DOI Creative Commons
Alessandro Galgani,

Marco Scotto,

Filippo Sean Giorgi

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(9), P. 10180 - 10199

Published: Sept. 14, 2024

Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that markedly precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson’s Alzheimer’s diseases. In humans, although tools have been developed to infer information on these nuclei, encompassing neuroimaging neurophysiological methods, a detailed specific direct evaluation their cellular features vivo has difficult obtain until recent years. The development induced pluripotent stem cell (iPSC) models allowed research deeply delve into molecular biology NSS neurons. fact, iPSCs can be produced easily non-invasively from patients’ fibroblasts or circulating blood monocytes, by de-differentiating those cells using protocols, then re-differentiated towards neural phenotypes, which may reproduce correspondent brain neurons (including ones) same patient. this review, we summarized findings obtained field NDDs iPSCs, with aim understand how reliably might represent vitro NSS. We found most current literature NSSs focused midbrain dopaminergic disease, providing interesting results pathophysiology even leading first human autologous transplantation. Differentiation protocols for noradrenergic, cholinergic, serotoninergic also recently defined published. Thus, it expected near future, approach could extend other NDDs.

Language: Английский

Citations

1