Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Novel PET/SPECT Imaging Probes for Diagnosis of Alzheimer’s Disease

Abstract

Abstract. Alzheimer's disease (AD) is a neurodegenerative disease of the brain associated with irreversible cognitive decline, memory impairment, and behavioral changes. Postmortem brains of AD patients reveal neuropathologic features, in particular the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), which contain β-amyloid peptides and highly phosphorylated tau proteins. Currently, AD can only be definitively confirmed by postmortem histopathologic examination of SPs and NFTs in the brain. Therefore, SPs and NFTs in the brain may be useful as biomarkers for the differential diagnosis of AD; the detection of individual SPs and NFTs in vivo by positron-emission tomography (PET) or single-photon emission computed tomography (SPECT) should improve diagnosis and also accelerate discovery of effective therapeutic agents for AD. Many PET/SPECT imaging probes for SPs have already been developed. Several of the PET probes have been shown in clinical trials to be useful for the imaging of β-amyloid plaques in living brain tissue. More recently, the development of PET/SPECT probes for in vivo imaging of NFTs is an active area of study in the field of molecular imaging because the appearance of NFT pathology correlates well with clinical severity of dementia. We will review current research on the development of PET/SPECT imaging probes for in vivo detection of SPs and NFTs and their application to diagnosis and therapy of AD.

Visual Reproduction on the Wechsler Memory Scale-Revised as a Predictor of Alzheimer’s Disease in Japanese Patients with Mild Cognitive Impairments

“…Further investigation is required to confirm the usefulness of those scores for the prediction of the conversion from MCI to AD in Japanese MCI patients. The compatibility of our diagnostic criteria for MCI with those used in other studies should be confirmed by pathologically confirmed markers, such as the decline of β-amyloid levels in cerebrospinal fluid, or elevation of brain β-amyloid deposition, which recently has come to be detectable by positron emission tomography [27]. …”

Molecular Approaches to the Treatment, Prophylaxis, and Diagnosis of Alzheimer’s Disease: Tangle Formation, Amyloid-β, and Microglia in Alzheimer’s Disease

“…Therefore, Aβ clearance from the brain as early as possible could be a primary target for therapeutic strategies in AD. For this purpose, the development of a method for early and precise diagnosis would be the most important step (56). In contrast, by the elucidation of the interaction between pathologies, novel targets for the diagnosis may be found, and the developmental opportunities and possibilities could be increased.…”

<i>In Vivo</i> Molecular Imaging

“…Thus we designed molecular probes for nuclear medicinal imaging the distribution of aggregates of Aβ and hyperphosphorylated tau protein in the brain of a patient with AD, which satisfied the following requirements: 1) high blood-brain barrier permeability; 2) high and specific binding ability to Aβ and tau aggregates; and 3) rapid elimination from normal regions of the brain. Consequently, we succeeded in developing 18 F-labeled pyridyl benzofuran derivative, 18 F-FPYBF-2, as a probe for PET imaging of Aβ plaques [28][29][30][31][32][33][34][35][36] and 123 I-labeled benzo imidazopyridine (BIP) derivative, BIP-3, as a probe for SPECT imaging of tau aggregates [37][38][39][40][41] (Fig. 3).…”