PET Imaging of Neuroinflammation in Alzheimer’s Disease

Abstract

Neuroinflammation play an important role in Alzheimer’s disease pathogenesis. Advances in molecular imaging using positron emission tomography have provided insights into the time course of neuroinflammation and its relation with Alzheimer’s disease central pathologies in patients and in animal disease models. Recent single-cell sequencing and transcriptomics indicate dynamic disease-associated microglia and astrocyte profiles in Alzheimer’s disease. Mitochondrial 18-kDa translocator protein is the most widely investigated target for neuroinflammation imaging. New generation of translocator protein tracers with improved performance have been developed and evaluated along with tau and amyloid imaging for assessing the disease progression in Alzheimer’s disease continuum. Given that translocator protein is not exclusively expressed in glia, alternative targets are under rapid development, such as monoamine oxidase B, matrix metalloproteinases, colony-stimulating factor 1 receptor, imidazoline-2 binding sites, cyclooxygenase, cannabinoid-2 receptor, purinergic P2X7 receptor, P2Y12 receptor, the fractalkine receptor, triggering receptor expressed on myeloid cells 2, and receptor for advanced glycation end products. Promising targets should demonstrate a higher specificity for cellular locations with exclusive expression in microglia or astrocyte and activation status (pro- or anti-inflammatory) with highly specific ligand to enable in vivo brain imaging. In this review, we summarised recent advances in the development of neuroinflammation imaging tracers and provided an outlook for promising targets in the future.

Aquaporin 4 is differentially increased and depolarized in association with tau and amyloid-beta

“…Removing senescent glial cells prevented tau-dependent pathology and cognitive decline in PS19 mice [111]. Early astrocytosis has been demonstrated by positron emission tomography tracers in both patients with AD and amyloidosis animal models [112][113][114][115][116][117][118]. Tau accumulates in hilar astrocytes of the dentate gyrus in postmortem brains from patients with AD [119][120][121] and induces neuronal dysfunction and memory deficits in a mouse model [122].…”

Rapamycin Attenuated Zinc-Induced Tau Phosphorylation and Oxidative Stress in Rats: Involvement of Dual mTOR/p70S6K and Nrf2/HO-1 Pathways

“…Advances in noninvasive imaging have enabled the of metal accumulation in vivo by using magnetic resonance imaging (107). A longitudinal study using in vivo imaging of the treatment effect on tau, neuroinflammation, and ROS in an animal model will provide further systematic insights (19,(108)(109)(110).…”

Recent Developments in Positron Emission Tomography Tracers for Proteinopathies Imaging in Dementia

“…The application of new disease-modifying treatment such as immunotherapy will likely require screening in prodromal patients for pathological evidence, e.g., cerebral Aβ, tau, or α-synuclein accumulation, and monitoring of treatment effects ( Sevigny et al, 2016 ; Boxer et al, 2019 ; Rabinovici et al, 2019 ). In addition, proteinopathy imaging combined with PET for synaptic loss, mitochondria dysfunction, and neuroinflammation (e.g., astrocytosis and microgliosis) enables a more comprehensive understanding of the mechanism underlying neurodegeneration associated with proteinopathies ( Calsolaro et al, 2021 ; Pascoal et al, 2021 ; Zhou R. et al, 2021 ).…”