Neuroimaging May Reveal How Alzheimer's Disease Develops

Current Alzheimer's disease (AD) research indicates that accumulation of amyloid-beta (Aß) protein plaques in the brain is central to the development of AD. Unfortunately, presence of these plaques is typically confirmed only at autopsy. Researchers are now utilizing positron emission tomography (PET) to image these plaques during life. This approach provides researchers with an opportunity to assess the amyloid hypothesis as it occurs in living patients.

In a review article in the journal Behavioral Neurology, 2009; Vol. 21, Issues 1-2, Dr. Gil Rabinovici and Dr. William Jagust from the University of California, San Francisco (UCSF; USA) and the University of California, Berkeley (USA), summarized the results of experiments from their laboratories and others using the Aß tracer Pittsburgh Compound-B (PIB). This compound binds to Aß protein and allows the mapping of plaques in the brains of AD and non-AD volunteer participants.

The investigators reported that PIB-PET can detect Aß deposits in a significant proportion of cognitively normal older subjects and that these deposits are associated with brain atrophy even in the absence of cognitive symptoms. By the time patients develop mild cognitive impairment (MCI), amyloid load in the brain appears to have reached a plateau. As patients progress to dementia, neurodegeneration and, cognitive decline proceed independently of further amyloid accumulation.

The authors interpret these results as consistent with a model in which amyloid deposition plays a critical early role on the path to AD, beginning years before onset of symptoms and triggering a series of events, which ultimately leads to cognitive decline and dementia.

While the use of PIB-PET is currently limited to research centers because of the compound's very short radioactive half-life (20 minutes), new amyloid imaging agents with longer half-lives are under development for more widespread use. Amyloid imaging is already playing an important role in the development of amyloid-based therapies for AD, and Dr. Rabinovici and Dr. Jagust speculated that in the future amyloid imaging would help clinicians in identifying patients with mild or atypical symptoms who may be candidates for antiamyloid treatments.

Writing in the article, the authors stated, "PIB-PET has provided us with our first in vivo glance at the dynamic relationship between amyloid deposition, clinical symptoms, and structural and functional changes in the brain in the continuum between normal aging and AD…In the future, Aß imaging will likely supplement clinical evaluation in selecting patients for antiamyloid therapies both during drug development and in the clinic.”

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