ABSTRACT
Alzheimer’s disease (AD) is one of the most studied illnesses in contemporary medicine as its medical burden on elderly populations, societies at large, and national health services is daunting (Lovestone, 2009; Weiner and Lipton, 2009). The lack of diseasemodifying prophylactic and therapeutic agents and the difficulties in diagnosing people at risk to develop AD, or already at preclinical, very early cognitive, or neuropsychiatric stages, continues to impose major medical challenges as it becomes clear that limited therapeutic benefits can be garnered when probable AD is diagnosed clinically. AD patients present substantial unmet medical need as disease-modifying agents have not been realized in spite of several decades of intense research and attempts
3.1 Introduction .................................................................................................. 103 3.2 Volumetric Brain Imaging in Alzheimer’s Disease: Computerized
Tomography and Magnetic Resonance Imaging .......................................... 105 3.2.1 Computerized Tomography (CT) ...................................................... 105 3.2.2 Magnetic Resonance Imaging (MRI) ............................................... 105
3.3 Functional and Molecular Imaging in Dementia: FDG-PET ....................... 106 3.4 Amyloid Plaques as a Target for Imaging..................................................... 107
3.4.1 11C-PIB .............................................................................................. 108 3.4.2 18F-Flutemetamol .............................................................................. 109 3.4.3 18F-Florbetaben ................................................................................. 110 3.4.4 18F-Florbetapir .................................................................................. 110 3.4.5 Role of Amyloid PET Imaging in Emerging Diagnostic Criteria
for AD ............................................................................................... 111 3.5 Amyloid Beta Cascade Elements (Aggregate) Imaging ............................... 112 3.6 Summary ...................................................................................................... 113 References .............................................................................................................. 113
for clinical development of therapeutic agents consuming billions of dollars. Over this background, leading researchers and institutes from academia, government, and industry have emphasized the need for focused efforts on translational medicine and biomarker discovery, development, and validation for AD (Khachaturian et al., 2010; Hampel et al., 2010; Petanceska et al., 2009). Indeed, major efforts are underway to identify biomarkers (genetic, genomic, biochemical, physiological) that might serve disease risk assessment, disease progression, and response to treatment. At this time, several biomarker studies are undergoing validation as surrogate biomarkers that may allow drug registration for treatment, diagnosis of subclinical disease, or identification of very early (pre-minimal cognitive impairment) MCI (Hampel et al., 2010; Borroni et al., 2006). Some of the difficulties in this regard are clearly the result of still insufficient understanding of the mechanisms that trigger the pathological processes of AD, maintain and amplify these processes along with temporal and confounding factors across the decades of AD evolution. Contemporary knowledge on putative mechanisms of AD focus on extracellular amyloid beta (Aβ) and the intracellular pathology associated with tau proteins (Kim et al., 2011; Shaw et al., 2011; Brunden et al., 2009), although many other molecular pathways (such as oxygen radicals, inflammatory mediators, neurotransmitters) continue to be studied (Shaw et al., 2011).
