Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays.

Introduction: Late-life mood disorders (LLMDs) may represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer's disease (AD) and non-AD tau pathologies in LLMD participants.

Methods: Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using F-florzolotau and C-Pittsburgh compound B.

Alterations of striatal phosphodiesterase 10 A and their association with recurrence rate in bipolar I disorder.

Phosphodiesterase 10 A (PDE10A), a pivotal element of the second messenger signaling downstream of the dopamine receptor stimulation, is conceived to be crucially involved in the mood instability of bipolar I disorder (BD-I) as a primary causal factor or in response to dysregulated dopaminergic tone. We aimed to determine whether striatal PDE10A availability is altered in patients with BD-I and assessed its relationship with the clinical characteristics of BD-I. This case-control study used positron emission tomography (PET) with 2-(2-(3-(4-(2-[F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([F]MNI-659), a radioligand that binds to PDE10A, to examine the alterations of the striatal PDE10A availability in the living brains of individuals with BD-I and their association with the clinical characteristics of BD-I.

Association between mammillary body atrophy and memory impairment in retired athletes with a history of repetitive mild traumatic brain injury.

Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled.

PET classification of tau pathologies in patients with frontotemporal dementia.

Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. neuropathological assessments of frontotemporal dementia at an individual level have hitherto not been successful. In this study, we aim to classify patients with frontotemporal dementia based on topologies of tau protein aggregates captured by PET with F-florzolotau (aka F-APN-1607 and F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer's disease as well as in non-Alzheimer's disease tauopathies.

Two pathways differentially linking tau depositions, oxidative stress, and neuronal loss to apathetic phenotypes in progressive supranuclear palsy.

Patients with progressive supranuclear palsy (PSP) frequently exhibit apathy but the neuropathological processes leading to this phenotype remain elusive. We aimed to examine the involvement of tau protein depositions, oxidative stress (OS), and neuronal loss in the apathetic manifestation of PSP. Twenty patients with PSP and twenty-three healthy controls were enrolled.

Positron Emission Tomography Assessments of Phosphodiesterase 10A in Patients With Schizophrenia.

Background And Hypothesis: Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels.

An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with F-PM-PBB3 (F-APN-1607).

Positron emission tomography (PET) with F-PM-PBB3 (F-APN-1607, F-Florzolotau) enables high-contrast detection of tau depositions in various neurodegenerative dementias, including Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). A simplified method for quantifying radioligand binding in target regions is to employ the cerebellum as a reference (CB-ref) on the assumption that the cerebellum has minimal tau pathologies. This procedure is typically valid in AD, while FTLD disorders exemplified by progressive supranuclear palsy (PSP) are characterized by occasional tau accumulations in the cerebellum, hampering the application of CB-ref.

A Machine Learning-Based Approach to Discrimination of Tauopathies Using [ F]PM-PBB3 PET Images.

Background: We recently developed a positron emission tomography (PET) probe, [ F]PM-PBB3, to detect tau lesions in diverse tauopathies, including mixed three-repeat and four-repeat (3R + 4R) tau fibrils in Alzheimer's disease (AD) and 4R tau aggregates in progressive supranuclear palsy (PSP). For wider availability of this technology for clinical settings, bias-free quantitative evaluation of tau images without a priori disease information is needed.

Objective: We aimed to establish tau PET pathology indices to characterize PSP and AD using a machine learning approach and test their validity and tracer capabilities.

Findings of F-PI-2620 tau PET imaging in patients with Alzheimer's disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions.

PET-based classification of corticobasal syndrome.

Introduction: Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS.

Methods: Sixteen CBS cases diagnosed by Cambridge's criteria and 12 cognitively healthy controls (HCs) underwent PET scans with C-PiB, C-PBB3, and F-FDG, along with T1-weighted magnetic resonance imaging.

First-in-human in vivo imaging and quantification of monoacylglycerol lipase in the brain: a PET study with F-T-401.

Purpose: Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-inflammatory arachidonic acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and anti-inflammatory agents. Although MAGL dysfunction has been implicated in neuropsychiatric disorders, it has never been visualized in vivo in human brain.

Evaluation of [F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies.

Tau aggregates represent a key pathologic feature of Alzheimer's disease and other neurodegenerative diseases. Recently, PET probes have been developed for detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer's disease tauopathies. The novel tau PET tracer, [F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer's disease and non-Alzheimer's disease tauopathies.

A first-in-human study of C-MTP38, a novel PET ligand for phosphodiesterase 7.

Purpose: Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand C-MTP38, which we recently developed, we aimed to image and quantify PDE7 in living human brains.

Differential associations of dopamine synthesis capacity with the dopamine transporter and D2 receptor availability as assessed by PET in the living human brain.

Background: The dopamine (DA) neurotransmission has been implicated in fundamental brain functions, exemplified by movement controls, reward-seeking, motivation, and cognition. Although dysregulation of DA neurotransmission in the striatum is known to be involved in diverse neuropsychiatric disorders, it is yet to be clarified whether components of the DA transmission, such as synthesis, receptors, and reuptake are coupled with each other to homeostatically maintain the DA neurotransmission. The purpose of this study was to investigate associations of the DA synthesis capacity with the availabilities of DA transporters and D2 receptors in the striatum of healthy subjects.

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies.

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD.

Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies.

Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR "magnetic resonance spectroscopy").