title: High throughput screens for the identification of compounds that alter the accumulation of the Alzheimer's amyloid beta peptide (Abeta).
abstract: Evidence gathered over the last two decades suggests that beta amyloid (Abeta), the predominant proteinaceous component of senile plaques, plays an early and critical role in the etiology and pathogenesis of Alzheimer's disease (AD). Thus, it is reasonable to hypothesize that compounds capable of reducing the accumulation of Abeta may be of value therapeutically. Additionally, compounds that influence Abeta accumulation may be useful as tools to further dissect the cellular pathways that regulate Abeta production and accumulation. To screen for compounds that affect Abeta levels, we have established high throughput, cell-based assays capable of the sensitive and selective detection of Abeta40 in parallel with the more amyloidogenic form of the peptide, Abeta42. To validate the approach, we examined the effects of several compounds previously identified to influence Abeta accumulation. Analysis of peptide accumulation following treatment with these compounds showed results similar to those previously published. Currently, we are using this assay to screen drugs that have already received FDA approval for the treatment of other diseases and over-the-counter natural product extracts. If compounds such as these can be identified that lower Abeta in the brain, they may represent one of the fastest and most cost effective methods to therapy.
authors.affiliation: Mayo Clinic Jacksonville, Birdsall Building Room 253, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Haugabook
authors.forename: D M
authors.initials: DM
authors.lastname: Yager
authors.forename: E A
authors.initials: EA
authors.lastname: Eckman
authors.forename: T E
authors.initials: TE
authors.lastname: Golde
authors.forename: S G
authors.initials: SG
authors.lastname: Younkin
authors.forename: C B
authors.initials: CB
authors.lastname: Eckman
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001681:Biological Assay / Q000295:instrumentation / Q000379:methods*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)