Molecular imaging in Alzheimer's disease: new perspectives on biomarkers for early diagnosis and drug development

Agneta Nordberg

doi:10.1186/alzrt96

Abstract

Recent progress in molecular imaging has provided new important knowledge for further understanding the time course of early pathological disease processes in Alzheimer's disease (AD). Positron emission tomography (PET) amyloid beta (Aβ) tracers such as Pittsburgh Compound B detect increasing deposition of fibrillar Aβ in the brain at the prodromal stages of AD, while the levels of fibrillar Aβ appear more stable at high levels in clinical AD. There is a need for PET ligands to visualize smaller forms of Aβ, oligomeric forms, in the brain and to understand how they interact with synaptic activity and neurodegeneration. The inflammatory markers presently under development might provide further insight into the disease mechanism as well as imaging tracers for tau. Biomarkers measuring functional changes in the brain such as regional cerebral glucose metabolism and neurotransmitter activity seem to strongly correlate with clinical symptoms of cognitive decline. Molecular imaging biomarkers will have a clinical implication in AD not only for early detection of AD but for selecting patients for certain drug therapies and to test disease-modifying drugs. PET fibrillar Aβ imaging together with cerebrospinal fluid biomarkers are promising as biomarkers for early recognition of subjects at risk for AD, for identifying patients for certain therapy and for quantifying anti-amyloid effects. Functional biomarkers such as regional cerebral glucose metabolism together with measurement of the brain volumes provide valuable information about disease progression and outcome of drug treatment.

Highlights

Alzheimer’s disease (AD) is characterized by a slow continued deterioration of cognitive processes
In the latter study it was evident at the individual level that increased, stable and decreased PIB retention were observed and the disease progression was reflected in significant decline in cerebral regional cerebral glucose metabolism and cognition [35]
We recently observed a significant increase in brain Pittsburgh Compound B (11C-PIB) retention in early mild cognitive impairment (MCI) patients when rescanned after 3 years [35]

Summary

Introduction

Alzheimer’s disease (AD) is characterized by a slow continued deterioration of cognitive processes. (atrophy, volume changes and cortical thickness) by magnetic resonance imaging, and to visualize and quantify brain pathology (fibrillar Aβ, tau, activated microglia and astrocytosis) as well as functional changes (cerebral glucose metabolism, neurotransmitter and neuroreceptor activity) by positron emission tomography (PET) (Table 1). In the latter study it was evident at the individual level that increased, stable and decreased PIB retention were observed and the disease progression was reflected in significant decline in cerebral regional cerebral glucose metabolism (rCMRglc) and cognition [35].

Results

Conclusion