NEURONAL EXPRESSION OF A SINGLE-CHAIN VARIABLE FRAGMENT ANTIBODY AGAINST ABETA OLIGOMERS AS A THERAPEUTIC APPROACH IN ALZHEIMER´S DISEASE

CERCATO MAGALÍ CECILIA; AMANDA SOUZA; JULIANA FORTUNA; JERUSALINSKY, DIANA ALICIA; MARÍA CLARA SELLÉS; ANDRE BITENCOURT; SERGIO FERREIRA

Encuentro; Advances in Alzheimer`s and Parkinson`s Therapies an AAT-AD/PD Focus Meetig; 2018

Alzheimer´s disease (AD) is the main cause of dementia in the elderly and is characterized by abnormal accumulation of the amyloid-beta peptide (Ab) in the brain. Considerable evidence indicates that soluble Ab oligomers (AbOs) are the neurotoxins implicated in synapse dysfunction and early memory loss in AD. We have investigated the therapeutic potential of NUsc1, a single-chain variable fragment (scFv) antibody that selectively targets AbOs. NUsc1 was originally selected in a screen to identify scFv?s targeting AβOs (Velasco et al., ACS Chem Neurosci 2013; Sebollela et al., J Neurochem 2017). Using an adeno-associated viral vector (AAV), we investigated the neuroprotective actions of NUsc1 in both in vitro and in vivo models of AD. The capacity of the AAV viral vector to drive the expression of NUsc1 in human neurons was further tested in human brain slices in culture.