PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research

Abstract

Alzheimer's Disease (AD), the leading cause of senile dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide and exerting tremendous socioeconomic burden on all societies. Although definitive diagnosis of AD is often made in the presence of clinical manifestations in late stages, it is now universally believed that AD is a continuum of disease commencing from the preclinical stage with typical neuropathological alterations appearing decades prior to its first symptom, to the prodromal stage with slight symptoms of amnesia (amnestic mild cognitive impairment, aMCI), and then to the terminal stage with extensive loss of basic cognitive functions, i.e., AD-dementia. Positron emission tomography (PET) radiotracers have been developed in a search to meet the increasing clinical need of early detection and treatment monitoring for AD, with reference to the pathophysiological targets in Alzheimer's brain. These include the pathological aggregations of misfolded proteins such as β-amyloid (Aβ) plagues and neurofibrillary tangles (NFTs), impaired neurotransmitter system, neuroinflammation, as well as deficient synaptic vesicles and glucose utilization. In this article we survey the various PET radiotracers available for AD imaging and discuss their clinical applications especially in terms of early detection and cognitive relevance.

PET Imaging in Animal Models of Alzheimer’s Disease

“…Nevertheless, due to the off-target binding to monoamine oxidase-B (MAO-B), the THK family tracers are deemed to have limited utility in imaging tauopathies in AD ( Ng et al, 2017 ; Murugan et al, 2019 ; Bao et al, 2021 ).…”

“…These tracers include [ 18 F]PI2620, [ 18 F]MK6240, [ 18 F]GTP1, [ 18 F]RO-948 (RO6958948), [ 18 F]JNJ311 (JNJ64349311), and [ 18 F]JNJ-067 (JNJ-64326067). Preliminary studies have been carried out in humans and healthy mice with promising results regarding the binding selectivity, affinity, and stability ( Bao et al, 2021 ). So far, these tracers have not been tested in AD animal models.…”

Cognitive Decline Assessment: A Review From Medical Imaging Perspective

“…The deposition of phospho-tau (p-tau) in the brain of CU individuals is an inevitable consequence of the aging process (Braak et al, 2011 ), following a specific neuropathological sequence (Braak's stages). Braak's stages are closely related to memory dysfunction, also reflecting the disease progression (Bao et al, 2021 ). The increased p-tau burden in cognitively healthy older adults must be carefully interpreted (Castellani, 2020 ).…”

Amyloid‐β protein and MicroRNA‐384 in NCAM‐Labeled exosomes from peripheral blood are potential diagnostic markers for Alzheimer's disease

“…Recent studies have shown that the increase and aggregation of Aβ outside the cells may not be the earliest molecular changes in AD. A series of molecular biological changes have begun to occur in neuronal cells before the occurrence of Aβ aggregation that can be detected by PET, which is considered the earliest (ultra‐early) change that leads to the occurrence, progression, and clinical onset of AD 5–7 . In recent years, with the conclusion of a number of large‐scale long‐term longitudinal studies, the clinical application value of multiple new familial AD ultra‐early diagnostic markers has been initially clarified.…”