Molecular Imaging in Sporadic Alzheimer's Disease Populations and Those Genetically at Risk

Abstract

The time course and order of the pathological-physiological processes in Alzheimer's disease (AD) are still under investigation and it is expected that molecular imaging will provide important insight into early brain pathology. Multi-tracer positron emission tomography studies visualizing fibrillar amyloid, inflammatory changes including astrocytosis and activation of microglia as well as cerebral glucose metabolism indicate that AD pathological processes are initiated and ongoing decades before the onset of cognitive symptoms. Therefore, prevention might be a new promising target for AD therapy.

Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study

“…Astrocytosis as measured by 11 C-DED PET was also observed to be negatively correlated with grey matter density in the parahippocampus at early prodromal AD stages [ 47 ]. Early 11 C-DED PET binding has also been reported in presymptomatic carriers of autosomal dominant AD mutations several decades before onset of symptoms and earlier than Aβ deposition [ 48 ]. Therefore, our findings of early 11 C-DED PET binding in APPswe mice before Aβ deposition are consistent with reported in vivo PET findings in humans, highlighting the translational aspects of this study.…”

Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease

“…Please refer to the review by Sompol and Norris (Sompol & Norris, 2018) PET-imaging is a powerful in vivo technique that uses selective and specific PET-tracers to monitor specific proteins, their location and density as well as metabolic processes in the body (Fowler et al, 2005). Thanks to recent advances in the field of in vivo biomarkers, different types of PET-tracers, CSF and plasma biomarkers are currently being used to track Aβ plaques, tau neurofibrillary tangles (NFTs), glucose metabolism, and neuroinflammatory processes (microglia and astrocytes activation) in AD and other proteinopathies (Nordberg, 2011(Nordberg, , 2014Perani et al, 2019;Rodriguez-Vieitez & Nordberg, 2018;Saint-Aubert et al, 2017). The recent approval…”

“…PET‐imaging is a powerful in vivo technique that uses selective and specific PET‐tracers to monitor specific proteins, their location and density as well as metabolic processes in the body (Fowler et al, 2005). Thanks to recent advances in the field of in vivo biomarkers, different types of PET‐tracers, CSF and plasma biomarkers are currently being used to track Aβ plaques, tau neurofibrillary tangles (NFTs), glucose metabolism, and neuroinflammatory processes (microglia and astrocytes activation) in AD and other proteinopathies (Nordberg, 2011, 2014; Perani et al, 2019; Rodriguez‐Vieitez & Nordberg, 2018; Saint‐Aubert et al, 2017). The recent approval of several new Aβ‐PET tracers in 2012 by the Food and Drug Administration (FDA), along with rapid progress in the development of tau‐tracers (Saint‐Aubert et al, 2017; Villemagne et al, 2018) and the FDA approval of first tau PET‐tracer flortaucipir or AV‐1451 (a radioactive diagnostic agent for the clinical PET‐imaging of NFTs in human brain (Jie et al, 2021)) in 2020, suggest that the field is moving rapidly.…”

Glial Asthenia and Functional Paralysis

“…These observations support the assumption that astrogliosis might be an early sign for histopathological changes in the course of AD and even might precede large deposition of fibrillar β-amyloid plaques in the brain. In presymptomatic AD mutations carriers high 11 C-DED binding is detected before amyloid plaques can be identified in the brain (Nordberg 2014). Recently, a significant negative correlation was observed between 11 C-DED binding and gray matter density in the parahippocampus in prodromal AD patients (Choo and others 2014).…”