Synaptic density affects clinical severity via network dysfunction in syndromes associated with frontotemporal lobar degeneration DOI Creative Commons
David J. Whiteside, Negin Holland, Kamen A. Tsvetanov

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 20, 2023

Abstract There is extensive synaptic loss from frontotemporal lobar degeneration, in preclinical models and human vivo post mortem studies. Understanding the consequences of for network function important to support translational guide future therapeutic strategies. To examine this relationship, we recruited 55 participants with syndromes associated degeneration 24 healthy controls. We measured density positron emission tomography using radioligand [ 11 C]UCB-J, which binds presynaptic vesicle glycoprotein SV2A, neurite dispersion diffusion magnetic resonance imaging, task-free imaging functional connectivity. Synaptic patients was reduced connectivity beyond atrophy. Functional moderated relationship between clinical severity. Our findings confirm importance syndromes, resulting effect on behaviour as a abnormal

Language: Английский

Detection and treatment of Alzheimer’s disease in its preclinical stage DOI
Michael S. Rafii,

Paul Aisen

Nature Aging, Journal Year: 2023, Volume and Issue: 3(5), P. 520 - 531

Published: May 18, 2023

Language: Английский

Citations

59
Detecting Early Cognitive Decline in Alzheimer’s Disease with Brain Synaptic Structural and Functional Evaluation DOI Creative Commons
Samo Ribarič

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 355 - 355

Published: Jan. 26, 2023

Early cognitive decline in patients with Alzheimer's (AD) is associated quantifiable structural and functional connectivity changes the brain. AD dysregulation of Aβ tau metabolism progressively disrupt normal synaptic function, leading to loss synapses, decreased hippocampal density early atrophy. Advances brain imaging techniques living have enabled transition from clinical signs symptoms-based diagnosis biomarkers-based diagnosis, techniques, quantitative EEG, body fluids sampling. The hippocampus has a central role semantic episodic memory processing. This function critically dependent on intrahippocampal connections many cortical regions, including perirhinal entorhinal cortex, parahippocampal association regions temporal parietal lobes, prefrontal cortex. Therefore, reflected altered intrinsic networks (aka large-scale networks), memory, default mode, salience networks. narrative review discusses recent critical issues related detecting AD-associated markers high-risk or neuropsychologically diagnosed subjective impairment mild impairment.

Language: Английский

Citations

23
In vivo imaging of synaptic density in neurodegenerative disorders with positron emission tomography: A systematic review DOI Creative Commons
M. de Visser, John T. O’Brien, Elijah Mak

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102197 - 102197

Published: Jan. 22, 2024

Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2 A (SV2A) enables quantification of density in the living human brain. Assessing regional distribution and severity loss will contribute our understanding pathological processes precede atrophy neurodegeneration. In this systematic review, we provide a discussion vivo SV2A PET imaging research for quantitative assessment various dementia conditions: amnestic Mild Cognitive Impairment Alzheimer’s disease, Frontotemporal dementia, Progressive supranuclear palsy Corticobasal degeneration, Parkinson’s disease Dementia Lewy bodies, Huntington’s Spinocerebellar Ataxia. We discuss main findings concerning group differences clinical-cognitive correlations, explore relations between other markers pathology. Additionally, touch upon healthy ageing outcomes radiotracer validation studies. Studies were identified on PubMed Embase 2018 2023; last searched 3rd July 2023. total 36 studies included, comprising 5 normal ageing, 21 clinical studies, 10 Extracted study characteristics participant details, methodological aspects, critical findings. summary, small but growing literature has revealed different spatial patterns among neurodegenerative disorders correlate cognitive functioning, supporting potential role differential diagnosis. shows tremendous capability novel insights into aetiology great promise as biomarker reduction. Novel directions future are proposed, including (a) longitudinal larger patient cohorts preclinical dementias, (b) multi-modal mapping onto processes, (c) monitoring therapeutic responses assessing drug efficacy trials.

Language: Английский

Citations

9
Emerging perspectives of synaptic biomarkers in ALS and FTD DOI Creative Commons

Karrthik Krishnamurthy,

Raj Kumar Pradhan

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Jan. 5, 2024

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions genetic mutations. Both involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated function or structure, offer insights into disease mechanisms, progression, treatment responses. These biomarkers can detect early, track its evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) blood, correlating progression. TDP-43 another key biomarker, mislocalization linked dysfunction. In FTD, tau studied as biomarkers. neuronal pentraxins (NPs), including pentraxin 2 (NPTX2), receptor (NPTXR), FTD pathology cognitive decline. Advanced technologies, machine learning (ML) artificial intelligence (AI), aid biomarker discovery drug development. Challenges this research include technological limitations detection, variability across patients, translating findings from animal models. ML/AI accelerate analyzing complex data predicting outcomes. early personalized strategies, mechanisms. While challenges persist, advancements interdisciplinary efforts promise revolutionize the understanding management FTD. This review will explore present comprehension discuss significance emphasize prospects obstacles.

Language: Английский

Citations

7
Synaptic vesicle glycoprotein 2A (SV2A) levels in the cerebral cortex in patients with Alzheimer's disease: a radioligand binding study in postmortem brains DOI
Jens D. Mikkelsen,

Sif Kaad,

Sanjay S. Aripaka

et al.

Neurobiology of Aging, Journal Year: 2023, Volume and Issue: 129, P. 50 - 57

Published: May 7, 2023

Language: Английский

Citations

14
Preliminary evidence for preserved synaptic density in late-life depression DOI Creative Commons
Thomas Vande Casteele, Maarten Laroy, Margot Van Cauwenberge

et al.

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 14, 2024

Abstract Late-life depression has been consistently associated with lower gray matter volume, the origin of which remains largely unexplained. Recent in-vivo PET findings in early-onset and Alzheimer’s Disease suggest that synaptic deficits contribute to pathophysiology these disorders may therefore volume late-life depression. Here, we investigate density vivo for first time using vesicle glycoprotein 2A receptor radioligand 11 C-UCB-J. We included 24 currently depressed adults (73.0 ± 6.2 years, 16 female, geriatric scale = 19.5 6.8) 36 age- gender-matched healthy controls (70.4 21 2.7 2.9) underwent simultaneous C-UCB-J positron emission tomography (PET) 3D T1- T2-FLAIR weighted magnetic resonance (MR) imaging on a 3-tesla PET-MR scanner. used analyses variance test binding volumes differences regions implicated The group showed trend hippocampus ( p 0.04), mesial temporal 0.02) prefrontal cortex compared control without surviving correction multiple comparison. However, no were found nor any associations between depressive symptoms. Our data suggests that, contrast Disease, is not changes. From therapeutic standpoint, preserved be an encouraging finding.

Language: Английский

Citations

5
Shock and kill within the CNS: A promising HIV eradication approach? DOI Creative Commons
Marieke M. Nühn, Stephanie B. H. Gumbs, Ninée V. E. J. Buchholtz

et al.

Journal of Leukocyte Biology, Journal Year: 2022, Volume and Issue: 112(5), P. 1297 - 1315

Published: Sept. 23, 2022

Abstract The most studied HIV eradication approach is the “shock and kill” strategy, which aims to reactivate latent reservoir by latency reversing agents (LRAs) allowing elimination of these cells immune-mediated clearance or viral cytopathic effects. CNS an anatomic compartment in (persistent) plays important role HIV-associated neurocognitive disorder. Restriction blood–brain barrier for maintenance homeostasis microenvironment, includes CNS-specific cell types, expression transcription factors, altered immune surveillance. Within predominantly myeloid such as microglia perivascular macrophages are thought be a persistent infection. Nevertheless, infection T astrocytes might also impact CNS. Genetic adaptation this microenvironment results genetically distinct, compartmentalized populations with differences profiles. Because profiles, LRAs have different effects within compared periphery. Moreover, reactivation brain complex could detrimental consequences. Finally, independent activity on HIV, themselves can adverse neurologic We provide extensive overview current knowledge strategy. Subsequently, we reflect promise strategy

Language: Английский

Citations

19
Substance use and spine density: a systematic review and meta-analysis of preclinical studies DOI
Henrique Nunes Pereira Oliva, Tiago Paiva Prudente, Eric J. Nunes

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: April 2, 2024

Language: Английский

Citations

4
From animal models to human individuality: Integrative approaches to the study of brain plasticity DOI Creative Commons

M. Hille,

Simone Kühn, Gerd Kempermann

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(21), P. 3522 - 3541

Published: Oct. 25, 2024

Language: Английский

Citations

4
eSylites: Synthetic Probes for Visualization and Topographic Mapping of Single Excitatory Synapses DOI
Christiane Huhn, Sheng‐Yang Ho, Clemens Schulte

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

The spatiotemporal organization of the postsynaptic density (PSD) is a fundamental determinant synaptic transmission, information processing, and storage in brain. major bottleneck that prevents direct precise representation nanometer-scaled excitatory glutamatergic synapses size antibodies, nanobodies, genetically encoded fluorescent tags. Here, we introduce small, high affinity synthetic probes for simplified, contrast visualization without limitations larger biomolecules. In vitro binding quantification together with microscopy-based evaluation identified eSylites, series bivalent peptides comprising dye, linker, sequence composition show remarkable cellular target selectivity. Applied on primary neurons or brain slices at nanomolar concentrations, eSylites specifically report PSD-95, key orchestrator glutamate receptor nanodomains juxtaposed to presynaptic release sites mediate fast transmission. eSylite design minimizes spatial dye offset thereby enables PSD-95 improved localization precision further time-resolved discrimination. particular, find individual dendritic spines can contain separate enriched either its closest homologues, PSD-93 SAP102. Collectively, these data establish as broadly applicable tool simplified synapse visualization, well high-end microscopy compatible probe resolving PSD unprecedented resolution.

Language: Английский

Citations

0