Plasma biomarkers in chronic single moderate-severe traumatic brain injury.

Blood biomarkers are an emerging diagnostic and prognostic tool that reflect a range of neuropathological processes following traumatic brain injury (TBI). Their effectiveness in identifying long-term neuropathological processes after TBI is unclear. Studying biomarkers in the chronic phase is vital because elevated levels in TBI might result from distinct neuropathological mechanisms during acute and chronic phases.

Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer's Disease: A Systematic Review.

Background: Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.

Objective: A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.

CenTauR: Toward a universal scale and masks for standardizing tau imaging studies.

Introduction: Recently, an increasing number of tau tracers have become available. There is a need to standardize quantitative tau measures across tracers, supporting a universal scale. We developed several cortical tau masks and applied them to generate a tau imaging universal scale.

Tau, β-Amyloid, and Glucose Metabolism Following Service-Related Traumatic Brain Injury in Vietnam War Veterans: The Australian Imaging Biomarkers and Lifestyle Study of Aging-Veterans Study (AIBL-VETS).

Traumatic brain injury (TBI) is common among military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer's disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 National Institute on Aging - Alzheimer's Association (NIA-AA) research framework, by measuring tau, β-amyloid, and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI.

Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease.

Background: Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD.

Rates of regional tau accumulation in ageing and across the Alzheimer's disease continuum: an AIBL F-MK6240 PET study.

Background: Tau positron emission tomography (PET) imaging enables longitudinal observation of tau accumulation in Alzheimer's disease (AD). F-MK6240 is a high affinity tracer for the paired helical filaments of tau in AD, widely used in clinical trials, despite sparse longitudinal natural history data. We aimed to evaluate the natural history of tau accumulation, and the impact of disease stage and reference region on the magnitude and effect size of regional change.

β-Amyloid and Tau Imaging in Chronic Traumatic Brain Injury: A Cross-sectional Study.

Background And Objectives: Traumatic brain injury (TBI) has been promoted as a risk factor for Alzheimer disease (AD). There is evidence of elevated β-amyloid (Aβ) and tau, the pathologic hallmarks of AD, immediately following TBI. It is not clear whether Aβ and tau remain elevated in the chronic period.

Exploring discordant low amyloid beta and high neocortical tau positron emission tomography cases.

Introduction: Neocortical 3R4R (3-repeat/4-repeat) tau aggregates are rarely observed in the absence of amyloid beta (Aβ). F-MK6240 binds specifically to the 3R4R form of tau that is characteristic of Alzheimer's disease (AD). We report four cases with negative Aβ, but positive tau positron emission tomography (PET) findings.

Visually Identified Tau 18F-MK6240 PET Patterns in Symptomatic Alzheimer's Disease.

Background: In Alzheimer's disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice.

Objective: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using 18F-MK6240, and whether these patterns are associated with different demographic and cognitive profiles.

Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer's continuum.

Introduction: We evaluated a new Simoa plasma assay for phosphorylated tau (P-tau) at aa217 enhanced by additional p-tau sites (p217+tau).

Methods: Plasma p217+tau levels were compared to F-NAV4694 amyloid beta (Aβ) positron emission tomography (PET) and F-MK6240 tau PET in 174 cognitively impaired (CI) and 223 cognitively unimpaired (CU) participants.

Results: Compared to Aβ- CU, the plasma levels of p217+tau increased 2-fold in Aβ+ CU and 3.

Mesial temporal tau in amyloid-β-negative cognitively normal older persons.

Background: Tau deposition in the mesial temporal lobe (MTL) in the absence of amyloid-β (Aβ-) occurs with aging. The tau PET tracer F-MK6240 has low non-specific background binding so is well suited to exploration of early-stage tau deposition. The aim of this study was to investigate the associations between MTL tau, age, hippocampal volume (HV), cognition, and neocortical tau in Aβ- cognitively unimpaired (CU) individuals.

First-in-Humans Evaluation of F-SMBT-1, a Novel F-Labeled Monoamine Oxidase-B PET Tracer for Imaging Reactive Astrogliosis.

Reactive gliosis, characterized by reactive astrocytes and activated microglia, contributes greatly to neurodegeneration throughout the course of Alzheimer disease (AD). Reactive astrocytes overexpress monoamine oxidase B (MAO-B). We characterized the clinical performance of F-()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (F-SMBT-1), a novel MAO-B PET tracer as a potential surrogate marker of reactive astrogliosis.

Assessing Reactive Astrogliosis with F-SMBT-1 Across the Alzheimer Disease Spectrum.

A neuroinflammatory reaction in Alzheimer disease (AD) brains involves reactive astrocytes that overexpress monoamine oxidase-B (MAO-B). F-()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (F-SMBT-1) is a novel F PET tracer highly selective for MAO-B. We characterized the clinical performance of F-SMBT-1 PET across the AD continuum as a potential surrogate marker of reactive astrogliosis.

PET Imaging of brain muscarinic receptors with F-Fluorobenzyl-Dexetimide: A first in human study.

M1 and M4 muscarinic receptor (mAChR) agonists are under development for the treatment of schizophrenia, Alzheimer's and Parkinson's disease. We performed first-in-human PET imaging of mAChR with F-Fluorobenzyl-Dexetimide (FDEX) in 10 healthy participants (29.4±4.

Incidence of idiopathic intracranial hypertension in Southern Tasmania, Australia.

Introduction: Anecdotally, the incidence of idiopathic intracranial hypertension (IIH) is increasing, linked to an increase in the obesity rate in Australian society. However, formal incidence and prevalence studies are rare. We therefore sought to determine the incidence and clinical features of IIH in Southern Tasmania, Australia.

Relationship between amyloid and tau levels and its impact on tau spreading.

Purpose: Previous studies have shown that Aβ-amyloid (Aβ) likely promotes tau to spread beyond the medial temporal lobe. However, the Aβ levels necessary for tau to spread in the neocortex is still unclear.

Methods: Four hundred sixty-six participants underwent tau imaging with [18F]MK6420 and Aβ imaging with [F]NAV4694.

Advances in Brain Amyloid Imaging.

Amyloid-β (Aβ) PET imaging has now been available for over 15 years. The ability to detect Aβ in vivo has greatly improved the clinical and research landscape of Alzheimer's disease (AD) and other neurodegenerative conditions. Aβ imaging provides very reliable, accurate, and reproducible measurements of regional and global Aβ burden in the brain.

Case Report: F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player.

It remains unclear if tau imaging may assist diagnosis of chronic traumatic encephalopathy (CTE). Flortaucipir PET has shown superior frontal with medial temporal tau binding consistent with the provisional neuropathological criteria for mid-stage CTE in group-level analyses of retired symptomatic NFL players and in one individual with pathologically confirmed CTE. F-MK6240 is a new PET ligand that has high affinity for tau.

Head-to-head comparison of cerebral blood flow single-photon emission computed tomography and F-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of Alzheimer disease.

Background: Clinical diagnosis of Alzheimer disease (AD) is only 70% accurate. Reduced cerebral blood flow (CBF) and metabolism in parieto-temporal and posterior cingulate cortex may assist diagnosis. While widely accepted that F-fluoro-2-deoxyglucose positron emission tomography ( F-FDG PET) has superior accuracy to CBF-SPECT for AD, there are very limited head-to-head data from clinically relevant populations and these studies relied on clinical diagnosis as the reference standard.

Meta-Analysis of Accuracy of the Spot Sign for Predicting Hematoma Growth and Clinical Outcomes.

Background and Purpose- The computed tomography angiographic spot sign refers to contrast leakage within intracerebral hemorrhage (ICH). It has been proposed as a surrogate radiological marker for ICH growth. We conducted a meta-analysis to study the accuracy of the spot sign for predicting ICH growth and mortality.