2004 Investigator-Initiated Research Grant

Diagnosing and monitoring Alzheimer’s disease depends primarily on assessing its effects on memory, thinking and behavior. Identifying a more concrete marker, or “biological fingerprint” of the disease might enable clinicians and scientists to diagnose the disease earlier, monitor progression, test disease-modifying drugs and assess treatment outcomes.

One key feature of Alzheimer’s disease that might serve as such a marker is a protein fragment called beta-amyloid. Although beta-amyloid’s exact role is not known, it appears to contribute to the breakdown of cell-to-cell communication and cell death as it accumulates in the Alzheimer brain.

In previous studies, Lee Goldstein, M.D., Ph.D., and his colleagues observed in genetically altered mice with Alzheimer-like brain disorders that concen-trations of beta-amyloid in the lens of the eye correspond with concentrations of the protein fragment in the brain. This accumulation of beta-amyloid in the lens is associated with an uncommon cataract that does not obscure vision.

The observations of cataracts were made with a sophisticated laser optical technology. The current effort is to refine this technology specifically for detecting amyloid-associated lens abnormalities and to test this second-generation laser optical system on the Alzheimer-like mice. The results from this work may lead to clinical trials to assess whether the amyloid-associated cataract can serve as a marker of brain amyloid levels and disease progression.