Maureen Handoko

     E-mail: hand0125@umn.edu

     Year Entered: 2005

     Degrees Received :
     College of St. Benedict
     Biochemistry major
     B.A.,  2005

     University of Minnesota
     Neuroscience Graduate Program
     Ph.D., 2012

     Honors and Awards:
     -Honors, Year 1, Medical School

     Thesis Advisor: Karen Hsiao-Ashe, M.D., Ph.D.

     Thesis Research: A growing body of evidence has led to the identification of a presymptomatic phase of Alzheimer’s disease (AD) wherein pathological processes occur prior to cognitive symptoms. The molecular agents that initiate these pathological processes are still unknown. Amyloid-β (Aβ) oligomers have been implicated in the pathophysiology of AD, and is thought to impair memory through mechanisms that involves the cytoskeletal protein tau. Aβ*56 and Aβ trimers are two soluble globular Aβ oligomers that have been shown to induce memory impairment in rodents in vivo and disrupt synaptic plasticity in brain slices, respectively. We hypothesize that these Aβ oligomers trigger tau abnormalities in humans. To test this hypothesis, we measured the levels of these Aβ oligomers in lumbar cerebrospinal fluid (CSF) from clinically characterized subjects. We found that both Aβ oligomers correlate very strongly with tau in the CSF of cognitively intact subjects. This finding is consistent with the hypothesis that Aβ oligomers may be driving tau abnormalities in presymptomatic AD, and that they may be molecular triggers for AD. We are currently conducting a follow-up study on a cohort of cognitively normal individuals who have been longitudinally followed to determine the predictive value of the levels of CSF Abeta oligomers for the development of cognitive impairment.