Earlier diagnosis for Alzheimer's
Scientists have come up with a promising approach that may allow an earlier diagnosis of Alzheimer's disease, thus allowing earlier therapeutic intervention.
Alzheimer's disease is characterized by the accumulation of amyloid b-protein plaques and neurofibrillary tangles in the brain. But at the moment, the only conclusive way to confirm the disease is by observing these tangles and plaques in brain sections-something that can be done only after a person has died.
Now, Joseph F. Poduslo and colleagues at the Mayo Clinic report on a technique for imaging Ab deposits in the living brain. Using a transgenic mouse model of Alzheimer's disease, the researchers show that some Ab deposits, namely neuritic-type plaques, can be radiolabeled in living tissue. They intravenously administered synthetic Ab radiolabeled with an isotope of iodine (125I) and found that it crossed the blood-brain barrier and bound to and labeled disease plaques.
The researchers also showed that permeability of the synthetic Ab protein across the blood-brain barrier can be increased by at least twofold through covalent modification with the naturally occurring polyamine chemical, putrescine. Moreover, synthetic Ab with this modification bound amyloid deposits with greater affinity than did unmodified Ab, although the researchers don't know why.
The results from these experiments support development of modified, radiolabeled Ab as a marker of amyloid deposition for use as a diagnostic tool for Alzheimer's disease in humans. However, although the results are encouraging, the researchers need to improve plaque labeling efficiency to achieve more widespread plaque labeling, perhaps through experiments with other probes or different types and modification of Ab protein, and use of 123I, an isotope that is more suitable for diagnostic imaging.
Research paper pp. 843-846
Research paper pp. 888-892
Research paper pp. 750-753 (July issue)
News & Views pp. 825-826
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