Open AccessNext generation tau models in Alzheimer's disease research – virus based gene delivery systems
Author(s) -
Veronika Cubinkova,
Bernadeta Valachova,
Veronika Brezováková,
Richard A. Szabo,
Ivana Zimova,
Z. Kostecká,
Santosh Jadhav
Publication year - 2017
Publication title -
acta virologica
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.412
H-Index - 33
eISSN - 1336-2305
pISSN - 0001-723X
DOI - 10.4149/av_2017_01_13
Subject(s) - neuroscience , transgene , disease , hippocampus , gene delivery , dementia , biology , amyloid (mycology) , genetically modified mouse , tau pathology , ectopic expression , adeno associated virus , genetic enhancement , alzheimer's disease , medicine , vector (molecular biology) , pathology , gene , recombinant dna , genetics
Alzheimer's disease (AD) the most common form of dementia is characterized by cognitive decline and progressive loss of neurons in the central nervous system. Despite huge scientific progress, there are only few animal models that recapitulate at least majority of the AD pathology and related symptomatology. Therefore, alternative methods to develop animal models for neurodegenerative diseases are constantly explored. Recently, recombinant adeno-associated viruses (AAVs) are widely used viral vectors in development of novel models for neurodegenerative diseases. AAV vectors expressing full length, mutant or truncated forms of tau demonstrate early and robust pathology characterized by AT8 positivity, NFT formation, motor and cognitive deficits. Furthermore, AAVs have been used in expression of tau in amyloid rodent models thus developing both lesions of amyloid and tau therefore recapitulating AD like features. Major advantage of AAV as a delivery system is the site specific expression of tau, mostly in hippocampus and cortex, and thus elimination of unwanted ectopic transgene expression. These novel models may help in better understanding of AD etiopathogenesis and provide a platform for development and testing of disease modifying drugs in preclinical efficacy studies.