Modeling Alzheimer's disease: From past to future

Claudia Saraceno, Stefano Musardo, Elena Marcello, Silvia Pelucchi, Monica Di Luca

Research output: Contribution to journalReview article

Abstract

Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells.

Original languageEnglish
Article numberArticle 77
JournalFrontiers in Pharmacology
Volume4 JUN
DOIs
Publication statusPublished - 2013

Fingerprint

Alzheimer Disease
Amyloid Precursor Protein Secretases
Amyloid beta-Protein Precursor
Amyloid
Animal Disease Models
Induced Pluripotent Stem Cells
Invertebrates
Neurology
Rodentia
Pathology
Mutation
Pharmaceutical Preparations
Population

Keywords

  • Alzheimer's disease
  • Amyloid
  • Animal models
  • Computational model
  • Secretases

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Saraceno, C., Musardo, S., Marcello, E., Pelucchi, S., & Di Luca, M. (2013). Modeling Alzheimer's disease: From past to future. Frontiers in Pharmacology, 4 JUN, [Article 77]. https://doi.org/10.3389/fphar.2013.00077

Modeling Alzheimer's disease : From past to future. / Saraceno, Claudia; Musardo, Stefano; Marcello, Elena; Pelucchi, Silvia; Di Luca, Monica.

In: Frontiers in Pharmacology, Vol. 4 JUN, Article 77, 2013.

Research output: Contribution to journalReview article

Saraceno, C, Musardo, S, Marcello, E, Pelucchi, S & Di Luca, M 2013, 'Modeling Alzheimer's disease: From past to future', Frontiers in Pharmacology, vol. 4 JUN, Article 77. https://doi.org/10.3389/fphar.2013.00077
Saraceno, Claudia ; Musardo, Stefano ; Marcello, Elena ; Pelucchi, Silvia ; Di Luca, Monica. / Modeling Alzheimer's disease : From past to future. In: Frontiers in Pharmacology. 2013 ; Vol. 4 JUN.
@article{e140b646d76e468da56467a15aef2bb7,
title = "Modeling Alzheimer's disease: From past to future",
abstract = "Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells.",
keywords = "Alzheimer's disease, Amyloid, Animal models, Computational model, Secretases",
author = "Claudia Saraceno and Stefano Musardo and Elena Marcello and Silvia Pelucchi and {Di Luca}, Monica",
year = "2013",
doi = "10.3389/fphar.2013.00077",
language = "English",
volume = "4 JUN",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Modeling Alzheimer's disease

T2 - From past to future

AU - Saraceno, Claudia

AU - Musardo, Stefano

AU - Marcello, Elena

AU - Pelucchi, Silvia

AU - Di Luca, Monica

PY - 2013

Y1 - 2013

N2 - Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells.

AB - Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells.

KW - Alzheimer's disease

KW - Amyloid

KW - Animal models

KW - Computational model

KW - Secretases

UR - http://www.scopus.com/inward/record.url?scp=84881645230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881645230&partnerID=8YFLogxK

U2 - 10.3389/fphar.2013.00077

DO - 10.3389/fphar.2013.00077

M3 - Review article

C2 - 23801962

AN - SCOPUS:84881645230

VL - 4 JUN

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - Article 77

ER -