Imaging synaptic density in ageing and Alzheimer's Disease with [18F]-SynVesT-1 DOI Creative Commons
Joseph Giorgio, David N. Soleimani‐Meigooni, Mustafa Janabi

et al.

Published: Oct. 26, 2024

Abstract Monitoring synaptic injury in neurodegenerative diseases may provide new insights into the evolution of degenerative process as well a potential mechanism to target for preservation function. Synaptic density imaging with PET is relatively approach this issue. However, there are remaining questions about technical approaches data analysis including reference region selection, and how specific phenotypic presentations symptoms Alzheimer’s Disease (AD) reflected alterations density. Methods Using an SV2A ligand radiolabeled 18 F isotope ([ F]-SynVesT-1) we performed sensitivity analyses determine optimal tissue modelling derive whole brain ratio images. these images from sample young adults, older patients varied AD then contrast regional vivo biomarkers. Result Reference optimisation concluded that cerebellar grey matter best deriving images, find strong inverse association between [ F]-SynVesT-1 uptake amyloid beta tau deposition. Finally, individuals lower temporal volume but higher show preserved performance on MMSE. Conclusions shows close pathology be possible marker resilience neurodegeneration.

Language: Английский

Tracing synaptic loss in Alzheimer's brain with SV2A PET‐tracer UCB‐J DOI Creative Commons
Amit Kumar, Miriam Scarpa, Agneta Nordberg

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2589 - 2605

Published: Feb. 16, 2024

Abstract INTRODUCTION Synaptic loss is an early prominent feature of Alzheimer's disease (AD). The recently developed novel synaptic vesicle 2A protein (SV2A) PET‐tracer UCB‐J has shown great promise in tracking AD. However, there have been discrepancies between the findings and a lack mechanistic insight. METHODS Here we report first extensive pre‐clinical validation studies for control (CN; n = 11) AD ( brains using multidimensional approach post‐mortem brain imaging techniques, radioligand binding, biochemical studies. RESULTS AND DISCUSSION We demonstrate that could target SV2A with high specificity depict at synaptosome levels regions compared to CNs. showed highest hippocampus followed descending order by frontal cortex, temporal parietal cerebellum. 3 H‐UCB‐J large brain‐section autoradiography cellular/subcellular fractions binding indicated potential off‐target interaction phosphorylated tau (p‐tau) species brains, which subsequent clinical implications Highlights positron emission tomography (PET)–tracer (AD) brains. control. Potential studies, warranting further investigations.

Language: Английский

Citations

14
Synapse vulnerability and resilience underlying Alzheimer’s disease DOI Creative Commons
Raquel N. Taddei, Karen Duff

EBioMedicine, Journal Year: 2025, Volume and Issue: 112, P. 105557 - 105557

Published: Jan. 31, 2025

Synapse preservation is key for healthy cognitive ageing, and synapse loss represents a critical anatomical basis of dysfunction in Alzheimer's disease (AD), predicting dementia onset, severity, progression. viewed as primary pathologic event, preceding neuronal brain atrophy AD. Synapses may, therefore, represent one the earliest clinically most meaningful targets neuropathologic processes driving AD dementia. The highly selective particularly vulnerable synapses while leaving others, termed resilient, largely unaffected. Yet, anatomic molecular hallmarks resilient populations their association with changes (e.g. amyloid-β plaques tau tangles) memory remain poorly understood. Characterising selectively may be to understanding mechanisms versus enable development robust biomarkers disease-modifying therapies

Language: Английский

Citations

1
Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers DOI Creative Commons
Dietmar Rudolf Thal, Koen Poesen, Rik Vandenberghe

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 14, 2025

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of amyloid-β peptide (Aβ) and intraneuronal accumulation abnormal phosphorylated tau (τ)-protein (p-τ). Most frequently, these hallmark lesions are accompanied other co-pathologies in brain that may contribute to cognitive impairment, such as vascular lesions, transactive-response DNA-binding protein 43 (TDP-43), and/or α-synuclein (αSyn) aggregates. To estimate extent AD patients, several biomarkers have been developed. Specific tracers target visualize Aβ plaques, p-τ αSyn pathology or inflammation positron emission tomography. In addition imaging biomarkers, cerebrospinal fluid, blood-based biomarker assays reflecting AD-specific non-specific processes either already clinical use development. this review, we will introduce pathological brain, related discuss what respective determined at post-mortem histopathological analysis. It became evident initial stages plaque not detected with currently available biomarkers. Interestingly, precedes deposition, especially beginning when unable detect it. Later, takes lead accelerates pathology, fitting well known evolution measures over time. Some still lack clinically established today, TDP-43 cortical microinfarcts. summary, specific for AD-related pathologies allow accurate diagnosis based on pathobiological parameters. Although current excellent pathologies, they fail which analysis required. Accordingly, neuropathological studies remain essential understand development early stages. Moreover, there an urgent need co-pathologies, limbic predominant, age-related encephalopathy-related modify interacting p-τ. Novel approaches vesicle-based cryptic RNA/peptides help better future.

Language: Английский

Citations

1
Higher level of [3H]UCB-J binding in ApoE Ɛ4 allele carriers with Alzheimer disease DOI Creative Commons
Jens D. Mikkelsen,

Phoebe Linde-Atkins,

Burcu Azak Pazarlar

et al.

Neuroscience Letters, Journal Year: 2025, Volume and Issue: 849, P. 138135 - 138135

Published: Feb. 1, 2025

Neuronal and synapse losses are seen under the progression of Alzheimer's disease (AD). Accordingly, binding to synaptic vesicle glycoprotein 2A (SV2A) using selective radioligand [3H]UCB-J was found be reduced in frontal cortex from patients with AD. We report here that reduction SV2A is highly significant only not carrying ApoE ɛ4 allele. By contrast, those individuals one or two alleles had levels different controls. Because ApoE4 an important genetic risk strongly linked late-onset AD, this study raises interesting new unexpected association SV2A, loss, function.

Language: Английский

Citations

0
Imaging Synaptic Density in Aging and Alzheimer Disease with [18F]SynVesT-1 DOI Creative Commons
Joseph Giorgio, David N. Soleimani‐Meigooni, Mustafa Janabi

et al.

Journal of Nuclear Medicine, Journal Year: 2025, Volume and Issue: unknown, P. jnumed.124.269005 - jnumed.124.269005

Published: March 6, 2025

Synaptic density imaging with PET is a relatively new approach to monitoring synaptic injury in neurodegenerative diseases. However, there are remaining technical and clinical questions, including questions on reference region selection how specific phenotypic presentations symptoms of Alzheimer disease (AD) reflected alterations density. Methods: Using vesicle glycoprotein 2A (SV2A) ligand radiolabeled the 18F isotope ([18F]SynVesT-1), we performed sensitivity analyses determine optimal tissue modeling derive whole-brain ratio images. these images from sample young adults, older patients varied AD, then contrasted regional SV2A vivo AD biomarkers. Results: Reference optimization concluded that cerebellar gray matter best for deriving images, found strong inverse association between [18F]SynVesT-1 uptake amyloid β tau deposition. Finally, individuals lower temporal volume but higher show preserved performance mini-mental state examination. Conclusion: shows close pathology, may be possible marker resilience neurodegeneration.

Language: Английский

Citations

0
Biomarkers in Alzheimer’s disease: Emerging trends and clinical implications DOI Creative Commons

Piaopiao Lian,

Yu Guo,

Jin‐Tai Yu

et al.

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer’s disease DOI Open Access

Faustine d’Orchymont

American Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2024, Volume and Issue: 14(1), P. 1 - 12

Published: Jan. 1, 2024

Language: Английский

Citations

2
Longitudinal synaptic loss versus tau Braak staging in amnestic mild cognitive impairment DOI Creative Commons
Greet Vanderlinden, Michel Koole, Laura Michiels

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Abstract INTRODUCTION The longitudinal progression of synaptic loss in Alzheimer's disease (AD) and how it is affected by tau pathology remains poorly understood. METHODS Thirty patients with amnestic mild cognitive impairment (aMCI) 26 healthy controls underwent evaluations tau, vesicle protein 2A (SV2A), amyloid positron emission tomography. Twenty‐one aMCI 2‐year follow‐up (FU) investigations. RESULTS Tau levels increased longitudinally Braak regions III through VI but not I II. SV2A decreased all aMCI. Baseline was negatively associated early at FU across regions. change were decline. DISCUSSION accumulation reaches a plateau already the stage AD. In regions, association between baseline might reflect dysfunction caused pathology. Highlights reached patients. show widespread decrease (SV2A) over 2 years. predictive for loss. tau–SV2A relation showed individual variability negative cognition.

Language: Английский

Citations

2
Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study DOI
Binyin Li,

Haijuan Chen,

Yingting Zheng

et al.

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2024, Volume and Issue: 52(1), P. 134 - 144

Published: Aug. 8, 2024

Language: Английский

Citations

1
Olive Oil Industry By-Products as a Novel Source of Biophenols with a Promising Role in Alzheimer Disease Prevention DOI Creative Commons
Marta Gonçalves, Marlene Costa, Fátima Paiva‐Martins

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(20), P. 4841 - 4841

Published: Oct. 12, 2024

This review explores the potential health benefits and applications of phenolic secoiridoids derived from olive oil by-products in prevention Alzheimer's disease (AD). As reviewed herein, polyphenols, such as epigallocatechin-3-gallate, epicatechin, resveratrol, show vitro vivo antioxidant, anti-inflammatory, neuroprotective properties, are particularly relevant context AD, a leading cause dementia globally. The industry, Mediterranean region, produces significant amounts waste, including leaves, pomace, wastewater, which pose environmental challenges but also offer an untapped source bioactive compounds. Despite promising studies indicating that olive-derived oleuropein hydroxytyrosol, may mitigate AD pathology, human clinical trials remain limited. variability extraction methods complex nature further complicate research. Future should focus on standardizing protocols conducting robust to fully assess therapeutic these approach not only supports development new treatments for promotes sustainability by valorizing industry waste.

Language: Английский

Citations

1