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

Targeting synapse function and loss for treatment of neurodegenerative diseases DOI
Borislav Dejanovic, Morgan Sheng, Jesse E. Hanson

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 23(1), P. 23 - 42

Published: Nov. 27, 2023

Language: Английский

Citations

50
The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration DOI Open Access
Anna Pisani, Fabiola Paciello, V. Del Vecchio

et al.

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(4), P. 652 - 652

Published: April 10, 2023

Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and sensory structures including olfactory auditory systems. Many studies have highlighted protective effects of BDNF brain, showing how it can promote neuronal growth survival modulate synaptic plasticity. On other hand, conflicting data about expression functions cochlear been reported. Several clinical experimental research showed alterations levels neurodegenerative diseases affecting peripheral system, suggesting that be promising biomarker most conditions, Alzheimer’s disease, shearing loss, or impairment. Here, we summarize current concerning brain domains (olfaction hearing), focusing on BDNF/TrkB signalling pathway activation both physiological pathological conditions. Finally, review significant highlighting possibility to target as early diagnosis cognitive neurodegeneration, opening new opportunities develop effective therapeutic strategies aimed counteract neurodegeneration.

Language: Английский

Citations

49
Application of Deep Learning for Prediction of Alzheimer’s Disease in PET/MR Imaging DOI Creative Commons
Yan Zhao, Qianrui Guo, Yukun Zhang

et al.

Bioengineering, Journal Year: 2023, Volume and Issue: 10(10), P. 1120 - 1120

Published: Sept. 24, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide. Positron emission tomography/magnetic resonance (PET/MR) imaging promising technique combines the advantages PET and MR to provide both functional structural information brain. Deep learning (DL) subfield machine (ML) artificial intelligence (AI) focuses on developing algorithms models inspired by structure function human brain's neural networks. DL has been applied various aspects PET/MR in AD, such as image segmentation, reconstruction, diagnosis prediction, visualization pathological features. In this review, we introduce basic concepts types algorithms, feed forward networks, convolutional recurrent autoencoders. We then summarize current applications challenges discuss future directions opportunities for automated diagnosis, predictions models, personalized medicine. conclude great potential improve quality efficiency new insights into pathophysiology treatment devastating disease.

Language: Английский

Citations

25
Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer’s disease DOI
Jie Wang, Qi Huang, Xing Chen

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(9), P. 2799 - 2809

Published: April 8, 2024

Language: Английский

Citations

13
APOE ε4 is associated with decreased synaptic density in cognitively impaired participants DOI Creative Commons
Kun He, Binyin Li, Jie Wang

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(5), P. 3157 - 3166

Published: March 13, 2024

Abstract INTRODUCTION We aimed to investigate the effect of apolipoprotein E4 ( APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18 F‐florbetapir and PET F‐SynVesT‐1. evaluated influence APOE allele investigated effects genotype associations Alzheimer's disease (AD) biomarkers. The mediation AD biomarkers ε4‐associated loss were analyzed. RESULTS Compared non‐carriers, carriers exhibited significant medial temporal lobe. Amyloid beta (Aβ) tau pathology mediated different extents. between regulated by genotype. DISCUSSION was associated decreased individuals may be driven

Language: Английский

Citations

12
The associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An 18F-SynVesT-1 PET/MR study DOI
Junpeng Li, Qi Huang, Na Qi

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: 44(7), P. 1199 - 1207

Published: Jan. 31, 2024

A newly developed SV2A radiotracer, 18 F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer’s disease (AD) “A/T/N” biomarkers. The included a cohort of 97 subjects, consisting 64 patients cognitive impairment (CI) 33 individuals normal cognition (CU). All subjects underwent F-SynVesT-1 PET/MR F-florbetapir PET/CT scans. Additionally, subgroup also F-MK-6240, F-FDG PET/CT, plasma Aβ42/Aβ40 p-tau181 tests. differences between the groups correlations AD biomarkers were analyzed. results showed that compared CU group, CI Aβ+ (CI+) group exhibited most pronounced synapse loss hippocampus, some observed neocortex. Furthermore, hippocampus parahippocampal gyrus associations detected by both imaging tests group. FDG uptake hippocampal volume CI+ In conclusion, demonstrated significant loss, as measured promising tracer close correlation clinical syndrome pathological changes.

Language: Английский

Citations

12
Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer’s disease: A [18F]PSS232 PET/MRI study DOI Creative Commons
Jie Wang, Yingfang He, Xing Chen

et al.

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

Published: Jan. 12, 2024

Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling relevant failure play a key role the initial pathophysiological mechanism of Alzheimer's disease (AD). The study aims to investigate association between availability AD's biomarkers cognitive function.

Language: Английский

Citations

11
Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment DOI Creative Commons
Jie Wang, Qi Huang, Kun He

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(6), P. 3876 - 3888

Published: April 18, 2024

Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling relevant failure play a key role the pathophysiological mechanism of Alzheimer's disease (AD).

Language: Английский

Citations

10
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
Linking white matter hyperintensities to regional cortical thinning, amyloid deposition, and synaptic density loss in Alzheimer's disease DOI Creative Commons
Junfang Zhang,

Haijuan Chen,

Jie Wang

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(6), P. 3931 - 3942

Published: April 22, 2024

We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid tau deposition, synaptic density in WMH-connected cortex using multimodal images.

Language: Английский

Citations

9