Detection of changes in synaptic density in amyotrophic lateral sclerosis patients using ¹⁸F‐SynVesT‐1 positron emission tomography

Abstract

Background and purpose: Synaptic loss is well established as the major correlate of characteristic and consistent pathology in amyotrophic lateral sclerosis (ALS). We aimed to assess the possible discriminant diagnostic value of 18 F-SynVesT-1 positron emission tomography (PET) as a marker of ALS pathology and investigate whether specific synaptic density signatures are present in ALS with different subtypes.Methods: Twenty-one patients with ALS and 25 healthy controls (HCs) were recruited.All participants underwent 18 F-SynVesT-1-PET. Synaptic density between ALS and HCs and between different ALS subgroups were compared. Correlation between synaptic density and clinical features in ALS was also analyzed.Results: Low uptake distribution was found in the group comprising 21 ALS patients as compared with HCs in the right temporal lobe and the bilateral inferior frontal gyrus, anterior cingulate, and hippocampus-insula region. We also found low uptake in the bilateral superior temporal gyrus, hippocampus-insula, anterior cingulate, and left inferior frontal gyrus in ALS patients with cognitive impairment compared to HCs. Furthermore, compared to spinal onset ALS, bulbar onset ALS showed low uptake in the bilateral cingulate gyrus and high uptake in the bilateral superior temporal gyrus and left occipital lobe.No significant result was found in correlation analysis.

In vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer’s disease

“…18 As an 18 F-labeled difluoro-analog of UCB-J, 18 F-SynVesT-1 has good properties similar to 11 C-UCB-J, which include high brain uptake, fast and reversible kinetics, and high specific binding. 19 It has been used in several neurological diseases, including amyotrophic lateral sclerosis 20 and focal cortical dysplasia type II. 21 In recent SV2A PET studies, Mecca et al found SV2A binding was widely reduced in medial temporal and neocortical brain regions in early AD compared to cognitively normal (CN) participants.…”

“…18 As an 18 F-labeled difluoro-analog of UCB-J, 18 F-SynVesT-1 has good properties similar to 11 C-UCB-J, which include high brain uptake, fast and reversible kinetics, and high specific binding. 19 It has been used in several neurological diseases, including amyotrophic lateral sclerosis 20 and focal cortical dysplasia type II. 21…”

SV2A PET imaging in human neurodegenerative diseases

“…A recent synaptic PET study using 18F-SynVesT-1 on 21 amyotrophic lateral sclerosis (ALS) patients and 26 heatlhy controls from China ( Tang et al, 2022 ) revealed lower uptake in the ALS group compared to controls in specific brain regions including the right temporal lobe, bilateral inferior frontal gyrus, anterior cingulate, and hippocampus–insula area. This study also observed reduced uptake in the bilateral superior temporal gyrus, hippocampus–insula, anterior cingulate, and left inferior frontal gyrus in ALS patients with cognitive impairment versus controls.…”

Bringing synapses into focus: Recent advances in synaptic imaging and mass-spectrometry for studying synaptopathy

“…Similarly, studies in Parkinson's, have used this technique to confirm synaptic loss in the substantia nigra, red nucleus and locus coeruleus, the main affected areas in PD (Matuskey et al, 2020) as well as to study overall cerebral synaptic density in primary tauopathies (Holland et al, 2022). In ALS, 18 F-SynVesT-1 PET (another SV2 radiomarker) was used to assess synaptic density changes in different areas of the brain (Tang et al, 2022) and importantly, the results closely aligned with previous post-mortem data (Henstridge et al, 2018). Moreover, SV2A PET has also been used in frontotemporal dementia (FTD), which is thought to exist on a disease spectrum with ALS, to study synaptic density changes in patients with behavioral variant FTD (Malpetti et al, 2023), and in carriers of a repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene, which has been linked to both ALS and FTD (Malpetti et al, 2021).…”