Toward alpha-synuclein seed amplification assay in clinical practice.

Introduction: Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility in routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents to facilitate its clinical implementation.

Charge detection mass spectrometry on human-amplified fibrils from different synucleinopathies.

Amyloid fibrils are self-assembled mesoscopic protein aggregates, which can accumulate to form deposits or plaques in the brain. amplification of fibrils can be achieved with real-time quaking-induced conversion (RT-QuIC). However, this emerging technique would benefit from a complementary method to assess structural properties of the amplification products.

Core cerebrospinal fluid biomarker profile in anti-LGI1 encephalitis.

Objective: To compare CSF biomarkers' levels in patients suffering from anti-Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis to neurodegenerative [Alzheimer's disease (AD), Creutzfeldt-Jakob's disease (CJD)] and primary psychiatric (PSY) disorders.

Methods: Patients with LGI1 encephalitis were retrospectively selected from the French Reference Centre database between 2010 and 2019 and enrolled if CSF was available for biomarkers analysis including total tau (T-tau), phosphorylated tau (P-tau), amyloid-beta Aβ1-42, and neurofilaments light chains (Nf L). Samples sent for biomarker determination as part of routine practice, and formally diagnosed as AD, CJD, and PSY, were used as comparators.

Coarticulatory Aspects of the Fluent Speech of French and Italian People Who Stutter Under Altered Auditory Feedback.

A number of studies have shown that phonetic peculiarities, especially at the coarticulation level, exist in the disfluent as well as in the perceptively fluent speech of people who stutter (PWS). However, results from fluent speech are very disparate and not easily interpretable. Are the coarticulatory features observed in fluent speech of PWS a manifestation of the disorder, or rather a compensation for the disorder itself? The purpose of the present study is to investigate the coarticulatory behavior in the fluent speech of PWS in the attempt to answer the question on its symptomatic or adaptive nature.

A multicenter cohort study to investigate the factors associated with functional autonomy change in patients with cognitive complaint or neurocognitive disorders: the MEMORA study protocol.

Background: The identification of factors associated with functional impairment, in particular those which are potentially modifiable, may help to delay the advanced stages of functional dependence in patients with neurocognitive disorders such as Alzheimer's disease and related disorders. The objectives of the MEMORA cohort are to investigate the factors associated, first with functional autonomy change over time, and secondarily with the cognitive performance and behavioral disorders changes over time.

Methods: The MEMORA study is a multicenter prospective cohort study carried out throughout the patient's care pathway, in Memory centers of Lyon (France).

Impact of Cognitive, Functional, Behavioral Disorders, and Caregiver Burden on the Risk of Nursing Home Placement.

Objectives: To estimate the attributable fraction of nursing home placement associated with cognitive impairment, neuropsychiatric symptoms, behavioral disorders, functional limitations, and caregiver burden.

Design: Longitudinal study conducted on the "MEMORA cohort" linked with both regional public health insurance and hospital discharge databases.

Setting: Memory center at the University Hospital of Lyon, France.

In Silico, in Vitro, and in Vivo Evaluation of New Candidates for α-Synuclein PET Imaging.

Accumulation of α-synuclein (α-syn) is a neuropathological hallmark of synucleinopathies. To date, no selective α-syn positron emission tomography (PET) radiotracer has been identified. Our objective was to develop the first original, selective, and specific α-syn PET radiotracer.

Amyloid-Beta Radiotracer [F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue.

The accumulation of aggregated alpha-synuclein (-syn) in multiple brain regions is a neuropathological hallmark of synucleinopathies. Multiple system atrophy (MSA) is a synucleinopathy characterized by the predominant cerebral accumulation of aggregated -syn as cytoplasmic glial inclusions (CGI). A premortem diagnosis tool would improve early diagnosis and help monitoring disease progression and therapeutic efficacy.

Hippocampal 5-HT receptor expression changes in prodromal stages of Alzheimer's disease: Beneficial or deleterious?

There is increasing evidence that the serotonergic system is highly dysfunctional in Alzheimer's disease (AD), and this could be related to cognitive impairments associated with dementia. Of the various serotonin receptors, 5-HT receptors are relevant to AD as they are highly expressed in the human hippocampus and are known to be involved in the regulation of memory processes. This review will discuss the involvement of 5-HT receptors in AD at several levels (post-mortem, in-vivo imaging, animal models).

Agonist and antagonist bind differently to 5-HT1A receptors during Alzheimer's disease: A post-mortem study with PET radiopharmaceuticals.

PET imaging studies using 5-HT1A receptor radiotracers show a decreased density of this receptor in hippocampi of patients with Alzheimer's disease (AD) at advanced stages. However, current 5-HT1A receptor radiopharmaceuticals used in neuroimaging are antagonists, thought to bind to 5-HT1A receptors in different functional states (i.e.

Differential effects of amyloid-beta 1-40 and 1-42 fibrils on 5-HT1A serotonin receptors in rat brain.

Evidence accumulates suggesting a complex interplay between neurodegenerative processes and serotonergic neurotransmission. We have previously reported an overexpression of serotonin 5-HT1A receptors (5-HT(1A)R) after intrahippocampal injections of amyloid-beta 1-40 (Aβ40) fibrils in rats. This serotonergic reactivity paralleled results from clinical positron emission tomography studies with [(18)F]MPPF revealing an overexpression of 5-HT(1A)R in the hippocampus of patients with mild cognitive impairment.

Binding of the PET radiotracer [¹⁸F]BF227 does not reflect the presence of alpha-synuclein aggregates in transgenic mice.

Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of many neurodegenerative diseases, collectively termed synucleinopathies. There is currently no pre-mortem diagnosis tool for these diseases. Although some compounds have been described as potential ligands for α-syn aggregates, no specific PET radiotracer of aggregated α-syn is currently available.

Prenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: a longitudinal small animal PET study using [(18)F]MK-9470.

Evidence suggests that there is a link between the endocannabinoid system (ECS) and neuropsychiatric illnesses, including schizophrenia. Whilst the ECS has been shown to be involved in immune system regulation in various ways, it is known that infections during pregnancy can modulate the immune system of the mother and increase the risk for schizophrenia in offspring. In animal studies, maternal immune activation following administration of viral or bacterial mimics has been shown to reproduce many key structural, behavioural, and pharmacological abnormalities in offspring that resemble schizophrenia.

Increases in [3H]muscimol and [3H]flumazenil binding in the dorsolateral prefrontal cortex in schizophrenia are linked to α4 and γ2S mRNA levels respectively.

Background: GABA(A) receptors (GABA(A)R) are composed of several subunits that determine sensitivity to drugs, synaptic localisation and function. Recent studies suggest that agonists targeting selective GABA(A)R subunits may have therapeutic value against the cognitive impairments observed in schizophrenia. In this study, we determined whether GABA(A)R binding deficits exist in the dorsolateral prefrontal cortex (DLPFC) of people with schizophrenia and tested if changes in GABA(A)R binding are related to the changes in subunit mRNAs.

Differential treatment regimen-related effects of HU210 on CB(1) and D(2)-like receptor functionality in the rat basal ganglia.

Background/aims: Functional linkages between the cannabinoid CB(1) and the dopaminergic systems have been reported although the observations and the mechanisms hypothesizing their interactions at the G protein-coupled receptor (GPCR) functionality level are conflicting.

Methods: Administration of a potent cannabinoid agonist, HU210, at various doses (25-100 μg/kg) and treatment regimens (1- to 14-day treatment) in rats was carried out to investigate the effect of HU210 treatment on the CB(1) and D(2)-like agonist-mediated GPCR activation.

Results: The desensitizations (reduced coupling) of both D(2) agonist- and CB(1) agonist-mediated GPCR activation was found to be treatment duration dependent and region specific, suggesting implication of receptor tolerance and adaptation due to the cannabinoid treatment.

Synergistic Effect between Maternal Infection and Adolescent Cannabinoid Exposure on Serotonin 5HT1A Receptor Binding in the Hippocampus: Testing the "Two Hit" Hypothesis for the Development of Schizophrenia.

Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5HT1A receptor binding (5HT1AR) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15.

Comparison of Cannabinoid CB(1) Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [F]MK-9470.

Despite the important role of cannabinoid CB(1) receptors (CB(1)R) in brain development, little is known about their status during adolescence, a critical period for both the development of psychosis and for initiation to substance abuse. In the present study, we assessed the ontogeny of CB(1)R in adolescent and adult rats in vivo using positron emission tomography with [(18)F]MK-9470. Analysis of covariance (ANCOVA) to control for body weight that would potentially influence [(18)F]MK-9470 values between the two groups revealed a main effect of age (F(1,109)=5.

Increased brain metabolism after acute administration of the synthetic cannabinoid HU210: a small animal PET imaging study with 18F-FDG.

Cannabis use has been shown to alter brain metabolism in both rat models and humans although the observations between both species are conflicting. In the present study, we examined the short term effects of a single-dose injection of the synthetic cannabinoid agonist HU210 on glucose metabolism in the rat brain using small animal (18)F-2-fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) 15 min (Day 1) and 24h (Day 2) post-injection of the agonist in the same animal. Young adult male Wistar rats received an intra-peritoneal injection of HU210 (100 μg/kg, n=7) or vehicle (n=5) on Day 1.

GABA(A) receptor density is altered by cannabinoid treatment in the hippocampus of adult but not adolescent rats.

Cannabinoids are known to induce transient psychotic symptoms and cognitive dysfunction in healthy individuals and contribute to trigger schizophrenia in vulnerable individuals, particularly during adolescence. Converging preclinical evidence suggests important interactions between cannabinoid and GABAergic systems. In the present study, we compared the effects of cannabinoid treatment on GABA(A) receptor binding in the brain of adolescent and adult rats.

Looking for a 5-HT7 radiotracer for positron emission tomography.

In search of a serotonin 5-HT(7) radiotracer for positron emission tomography, we developed 1-[2-[(2S)-1-(phenylsulfonyl)pyrrolidin-2-yl]ethyl]piperidin-4-yl 4-fluorobenzoate. After labeling in good yield with fluorine-18 via nitro for fluorine exchange, preliminary biological experiments with autoradiographies failed to evidence any specific 5-HT(7) receptor delineation.

[18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging.

Purpose: The serotonin-1A (5-HT(1A)) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT(1A) receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT(1A) receptors.

Effects of amyloid-β peptides on the serotoninergic 5-HT1A receptors in the rat hippocampus.

A recent [(18)F]MPPF-positron emission tomography study has highlighted an overexpression of 5-HT(1A) receptors in the hippocampus of patients with mild cognitive impairment compared to a decrease in those with Alzheimer's disease (AD) [Truchot, L., Costes, S.N.

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer.

Background: The Pittsburgh compound-B ([11C]PIB) is a highly interesting radiotracer for imaging amyloid plaques in Alzheimer's disease by positron emission tomography (PET). An increasing number of PET centres schedule its transfer for clinical studies and therefore are interested in its automated synthesis.

Method: With the aim of flexibility, we reported the first fully automated synthesis of [11C]PIB with the coupling of two commercial synthesizers.

The potential of a radiosensitive intracerebral probe to monitor 18F-MPPF binding in mouse hippocampus in vivo.

Unlabelled: As mouse imaging has become more challenging in preclinical research, efforts have been made to develop dedicated PET systems. Although these systems are currently used for the study of physiopathologic murine models, they present some drawbacks for brain studies, including a low temporal resolution that limits the pharmacokinetic study of radiotracers. The aim of this study was to demonstrate the ability of a radiosensitive intracerebral probe to measure the binding of a radiotracer in the mouse brain in vivo.

Unchanged density of 5-HT(1A) autoreceptors on the plasma membrane of nucleus raphe dorsalis neurons in rats chronically treated with fluoxetine.

5-HT(1A) autoreceptors regulate the firing of 5-HT neurons and their release of 5-HT. In previous immuno-electron microscopic studies, we have demonstrated an internalization of 5-HT(1A) autoreceptors in the nucleus raphe dorsalis (NRD) of rats, after the acute administration of a single dose of the specific agonist 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT) or of the selective 5-HT reuptake inhibitor, fluoxetine. Twenty-four hours after either treatment, the receptors were back in normal density on the plasma membrane of NRD neurons.