2011 Awardees
Haihao Zhu, PhD
Insulin Degrading Enzyme, Peripheral Monocytes and AD
Sporatic AD patients are shown to have impaired Abeta clearance, but not increased Abeta production, in the central nervous system (CNS). Insulin degrading enzyme (IDE) is the major extracellular protease degrading Abeta and lack of IDE activity exacerbates the AD pathology in the brain. Our preliminary study established an immunocapture assay to measure IDE activity in human serum and showed that compared to the elderly who had normal cognition, those with amnestic mild cognitive impairment (MCI) and probable AD had lower serum IDE degradation in a homebound elderly population. Peripheral monocytes/macrophages express IDE and are involved in AD pathogenesis in the brain. We thus hypothesize that using another study sample, BU ADC subjects, we will find that the elderly with probable AD or amnestic MCI have lower serum IDE activity than those with normal cognition. Decreased Abeta clearance by monocytes/macrophages, through the expression of IDE, will be linked with the diagnosis of AD.
Joseph Zaia, PhD
The Structure of Heparin Sulfate in AD Plaques Matter in Older adult with Alzheimer’s Disease of AD & PTSD
The presence of heparan sulfate (HS) glycosaminoglycans is a hallmark of Alzheimer’s disease plaques. HS is associated with neuritic plaques and promotes aggregation of the amyloid β (Aβ)-peptide. By contrast, HS inhibits the β-amyloid precursor protein cleaving enzyme-1 (BACE1) that acts on the amyloid precursor protein (APP) and is the rate limiting step in the formation of Aβ. These contrasting activities arise because the structure of HS is specific to cell type and temporal regulatory factors. Little is known about the fine structure of HS in Aβ plaques relative to normal brain tissue. In order to establish structural functional relationships, detailed structural analysis is necessary. The goal of this pilot study is to generate structural information on HS in Aβ-plaques and normal brain histological sections to inform Alzheimer’s disease treatment strategies. This effort will include characterization of HS structure associated with Aβ plaques observed in histological slides from brains of Alzheimer’s patients and controls. This ork will inform efforts to develop anti-amyloidosis therapeutics based on HS structures. RELEVANCE