The Development of a High Throughput Whole Brain Alzheimer's Disease Drug Screening Pipeline

Project Summary Alzheimer s diseaseADis a debilitating neurodegenerative disease affecting roughlyinpeople over the age ofInthe total cost of AD in the United States was estimated at $billion and is predicted to climb to $trillion by the yearDespite enormous efforts invested in finding a cureit has proven extremely difficult to develop treatments for ADContributing factors behind this difficulty is that AD is a complexmultifactorial diseaseoccurring over decadesand as CNS diseaseis very difficult to study directly in the clinicTo address this challengetheAD research summit set a goal to create and characterize a new generation of improved research models that would more faithfully reflect AD in humansThese new models hold enormous promisebut unfortunately contemporary tools are incomplete at bestPhenotypic whole brain methodologieswhile providing a critical overview of the temporal and spatial progression of ADhave little corresponding molecular informationMeanwhilein depth molecular methods remain confined to studying small portions of the brain due to time or cost limitationsThis lack of an overview of the molecular mechanisms driving the spread of AD across the braina central aspect of AD in humansleaves a crucial gap in our understanding of the etiology of the progression of AD and hinders the development of effective treatmentsTo bridge this gapthis proposal will build a flexible imaging and tissue processing platform to rapidly characterize AD rodent models that provides whole brain information while at the same time extends access to in depth molecular information to facilitate crucial clinical translatabilityThis proposal combines teams from TissueVision and the NIA funded MODEL AD Center at The Jackson Laboratory who are experts in neuroscienceoptical microscopyimaging assaysand who have a successful commercialization historyTogetherwe will build on a set of impressive preliminary results mapping AD progression in whole brain datasets and produce a drug development pipeline to provide automated brain region mapping and combinatorial markers of AD pathologyWe believe the synergy between instrumentationbiological assay developmentand the next generation of AD research models represents an ideal partnership to develop next generation tools that hold the promise of finally developing effective treatments for AD We propose to develop a novel whole brain imaging platform to rapidly screen Alzheimer s DiseaseADresearch modelsThe platform will identify regions of disease activity across the entire brain while at the same time allow researchers to interrogate the molecular mechanisms driving the spread of ADIt will provide researchers with a standardized framework allowing them to rapidly draw quantitativedetailed conclusions across therapeutic interventions and across rodent modelsand ultimately make informed decisions on clinical translatability of potential therapeutics