Critical Review of the Alzheimer’s Disease Non-Transgenic Models: Can They Contribute to Disease Treatment?

Issue title: Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America

Guest editors: K.S. Jagannatha Rao, Gabrielle B. Britton, Luisa Lilia Rocha Arrieta, Norberto Garcia-Cairasco, Alberto Lazarowski, Adrián Palacios, Antoni Camins Espuny and Ricardo B. Maccioni

Article type: Review Article

Authors: Flores-Cuadra, Julio A.^a | Madrid, Alanna^a | Fernández, Patricia L.^b | Pérez-Lao, Ambar R.^a | Oviedo, Diana C.^{a; c} | Britton, Gabrielle B.^a | Carreira, Maria B.^{a; *}

Affiliations: [a] Centro de Neurociencias, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panamá, República de Panamá | [b] Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Panamá, República de Panamá | [c] Escuela de Psicología, Facultad de Ciencias Sociales, Universidad Católica Santa María La Antigua (USMA), Panamá

Correspondence: [*] Correspondence to: Maria B. Carreira, PhD, Center for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), República de Panamá, Ciudad de Panamá. Tel.: +507 517 0700; E-mail: mcarreira@indicasat.org.pa.

Abstract: Alzheimer’s disease (AD) is a growing neurodegenerative disease without effective treatments or therapies. Despite the use of different approaches and an extensive variety of genetic amyloid based models, therapeutic strategies remain elusive. AD is characterized by three main pathological hallmarks that include amyloid-β plaques, neurofibrillary tangles, and neuroinflammatory processes; however, many other pathological mechanisms have been described in the literature. Nonetheless, the study of the disease and the screening of potential therapies is heavily weighted toward the study of amyloid-β transgenic models. Non-transgenic models may aid in the study of complex pathological states and provide a suitable complementary alternative to evaluating therapeutic biomedical and intervention strategies. In this review, we evaluate the literature on non-transgenic alternatives, focusing on the use of these models for testing therapeutic strategies, and assess their contribution to understanding AD. This review aims to underscore the need for a shift in preclinical research on intervention strategies for AD from amyloid-based to alternative, complementary non-amyloid approaches.

Keywords: Dementia, disease models, drug discovery, rodents

DOI: 10.3233/JAD-200870

Journal: Journal of Alzheimer's Disease, vol. 82, no. s1, pp. S227-S250, 2021