PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations.

Introduction: Individuals with Down syndrome (DS) have a high prevalence of Alzheimer's disease (AD) and reveal an earlier age of amyloid beta (Aβ) onset compared to sporadic AD. Differences in amyloid accumulation rates between DS and sporadic AD populations have not been established.

Methods: Participants with ≥ 3 [C-11]PiB scans (spanning > 6 years) and transitioning to Aβ+ were included, resulting in 20 DS and 23 neurotypical (NT) participants.

Examining the association between synaptic density and neurofibrillary tau among cognitively impaired and unimpaired older adults with and without Alzheimer's disease pathology.

Introduction: Synapse loss is a key driver of cognitive decline in Alzheimer's disease (AD), yet its direct relationship with neurofibrillary tau tangle (NFT) burden remains unclear. This study leveraged positron emission tomography (PET) imaging to investigate the link between NFT accumulation and synaptic density in older adults with and without AD pathology.

Methods: Older adults (N = 94) underwent PET imaging to quantify synaptic density ([C]UCB-J distribution volume ratio [DVR]), Aβ plaque burden ([C]PiB DVR), and NFT burden ([F]MK-6240 standardized uptake value ratio).

The striatum is an early, accurate indicator of amyloid burden using [C]PiB in Down syndrome: Comparison of two radiotracers.

Introduction: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [C]Pittsburgh Compound-B (PiB) positron emission tomography (PET) imaging, which has not been replicated with [F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.

Methods: Longitudinal PiB (n = 175 participants) and FBP (n = 92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome (ABC-DS) were used to measure cortical and striatal binding.

Evaluating the effect of extra-cerebral off-target binding in [F-18]MK6240 PET scans in early-stage Alzheimer's disease.

[F-18]MK6240 is a Positron Emission Tomography (PET) radioligand with favorable imaging characteristics for measuring tau aggregation in Alzheimer's disease (AD). In this study, we investigated the impact of extra-cerebral off-target binding (ECB) in the meninges and sinus present in [F-18]MK6240 PET scans on quantifying tau burden in preclinical AD. Based on large cohort data from 433 [F-18]MK6240 scans acquired at the University of Wisconsin-Madison, simulations were conducted to examine the range of effects of ECB by varying the ECB profile and input radiotracer concentration curves on areas of early tau accumulation in AD.

Measurement of synaptic density in Down syndrome using PET imaging: a pilot study.

Down syndrome (DS) is the most prevalent genetic cause of intellectual disability, resulting from trisomy 21. Recently, positron emission tomography (PET) imaging has been used to image synapses in vivo. The motivation for this pilot study was to investigate whether synaptic density in low functioning adults with DS can be evaluated using the PET radiotracer [C]UCB-J.

Age- and sex-related differences in human α4β2* nicotinic acetylcholine receptor binding evaluated with [F]nifene PET.

Neuronal α4β2* nicotinic acetylcholine receptors (nAChRs) are stimulated by nicotine and are associated with tobacco dependence. [F]Nifene is a PET radiotracer with high specificity for α4β2* nAChRs that can be used to investigate nAChR distribution in the human brain . In this study, we investigate the dependence of sex and age on the binding of [F]nifene in nonsmoking healthy human participants.

DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates.

Anxiety disorders are among the most prevalent psychiatric disorders, with symptoms often beginning early in life. To model the pathophysiology of human pathological anxiety, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in a nonhuman primate model of anxious temperament to selectively increase neuronal activity of the amygdala. Subjects included 10 young rhesus macaques; 5 received bilateral infusions of AAV5-hSyn-HA-hM3Dq into the dorsal amygdala, and 5 served as controls.

Alternative strategies for the synthesis of [C]ER176 for PET imaging of neuroinflammation.

[C]ER176 is a next generation PET radioligand for imaging 18 kDa translocator protein, a biomarker for neuroinflammation. The goal of this work was to investigate alternative strategies for the radiochemical synthesis, purification, and formulation of [C]ER176. An optimized tri-solvent high-performance liquid chromatography (HPLC) protocol is described to separate the hydro-de-chlorinated byproduct from [C]ER176.

Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders.

Non-human primate (NHP) models are essential for developing and translating new treatments that target neural circuit dysfunction underlying human psychopathology. As a proof-of-concept for treating neuropsychiatric disorders, we used a NHP model of pathological anxiety to investigate the feasibility of decreasing anxiety by chemogenetically (DREADDs [designer receptors exclusively activated by designer drugs]) reducing amygdala neuronal activity. Intraoperative MRI surgery was used to infect dorsal amygdala neurons with AAV5-hSyn-HA-hM4Di in young rhesus monkeys.