James A. Mortimer, Ph.D.

Markers for Pre-Clinical Alzheimer's Disease in an At-Risk Population Sample

Numerous studies show that AD begins at least 20 years before a clinical diagnosis of dementia can be made. In addition, about 30% of individuals who meet neuropathologic criteria for AD at autopsy remain non-demented during life', suggesting that the disease can reach an advanced stage without symptoms. Especially for cases where the disease is assymtomatic only in its early stages it will be important to be able to detect early AD specific proteins as early as possible to maximize the treatment. Although several individual biomarkers have been identified that predict AD development, some as much as 20 years prior to disease onset, little is known regarding how combinations of biomarkers can be used to identify asymptomatic persons at risk.

We propose to conduct a study to determine how putative markers of AD cluster in non-demented individuals. The study will utilize an existing longitudinally-studied, non-demented older cohort to determine whether there exist two or more groups of individuals, one with an aggregation of markers suspected to be associated with AD and the other with a paucity of such markers. The cohort is representative of adults initially aged 60 to 85 living in two census tracts of Charlotte County, Florida, who survived 5 years after baseline.

The proposed study will provide data on which markers best identify the purported individuals at very high risk of AD, providing vital preliminary findings relevant to the selection of efficient and inexpensive screening tests for pre-clinical AD. Finally, the study will provide preliminary data for a larger planned intervention study to prevent AD in initially non-demented individuals.