Alzheimer's disease is diagnosed definitively by the presence of amyloid and tau pathology in the context of dementia. Because plaques and tangles (the canonical AD lesions) can be detected with certainty only by histological analysis, a method of visualizing either or both of these lesions non-invasively in the living brain would be a boon to patients, physicians, and researchers. In vivo imaging would permit a longitudinal analysis of the amplification and spread of the lesions, as well as the relationship of the lesions to specific behavioral impairments; Furthermore, the ability to detect Aβ plaques early in the course of the illness could help to rule out other causes of cognitive decline, and the amyloid signal would be invaluable as a biomarker for assessing the effects of disease-modifying treatments for AD. At present, the most promising imaging method for AD is a PET method using radiolabeled Pittsburgh compound-B. The drawbacks of this method are the exposure of the patient to radiation, short half-life of the compound's radioactivity, expense, low...  Read more

Alzheimer's disease is diagnosed definitively by the presence of amyloid and tau pathology in the context of dementia. Because plaques and tangles (the canonical AD lesions) can be detected with certainty only by histological analysis, a method of visualizing either or both of these lesions non-invasively in the living brain would be a boon to patients, physicians, and researchers. In vivo imaging would permit a longitudinal analysis of the amplification and spread of the lesions, as well as the relationship of the lesions to specific behavioral impairments; Furthermore, the ability to detect Aβ plaques early in the course of the illness could help to rule out other causes of cognitive decline, and the amyloid signal would be invaluable as a biomarker for assessing the effects of disease-modifying treatments for AD. At present, the most promising imaging method for AD is a PET method using radiolabeled Pittsburgh compound-B. The drawbacks of this method are the exposure of the patient to radiation, short half-life of the compound's radioactivity, expense, low resolution, background noise and (from a research standpoint) the relatively poor binding of the compound to Aβ deposits in experimental transgenic mice.

The ideal imaging technique, then, would be safe, sensitive, specific, uncomplicated and inexpensive; comparable binding in humans and animal models also would be a plus. While we are still far from the ultimate imaging method, Higuchi et al. make important advances in several of these domains. Specifically, they have developed a non-radioactive, 19F-containing compound (FSB) that crosses the blood-brain barrier, binds selectively to amyloid deposits in transgenic mouse brain, and can be visualized by MRI both in the 19F and 1H modes. The compound is comparatively safe, selective, long-lived, and works well in a transgenic murine model of cerebral β-amyloidosis. The brain structures affected can be visualized with high resolution MRI. As the authors note, there is still need for improvement before this method becomes practical for use in humans. Relatively long imaging times in a powerful (9.4T) magnet are employed to achieve the reported results in mice. The differential sensitivity of T1-weighted 1HMRI for detecting plaques in different brain areas requires further analysis, and the sensitivity of the protocol for diffuse vs. dense deposits as well as for vascular β-amyloid in vivo is unclear. It would also be useful to know if the compound, or similar compounds, binds to pre-fibrillar Aß structures. Higuchi and colleagues note that experiments are in progress to assess the binding of the compound to tangle-like lesions in a mouse model of tauopathy. As a bridge between mice and humans, MR imaging of FSB could be profitably undertaken in larger animals such as aged nonhuman primates, which naturally develop senile plaques and cerebral amyloid angiopathy (and, in some instances, tauopathy). It is heartening to note the acceleration of progress in imaging AD pathology in vivo; it appears likely that clinicians and scientists soon may have multiple options for visualizing proteopathic lesions in the living brain.

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