TY - JOUR
T1 - Progressive impairments in executive function in the APP/PS1 model of Alzheimer's disease as measured by translatable touchscreen testing
AU - Shepherd, Amy
AU - Lim, Jeremiah K K.H.
AU - Wong, Vicky H H.Y.
AU - Zeleznikow-Johnston, Ariel M M.
AU - Churilov, Leonid
AU - Nguyen, Christine T T.O.
AU - Bui, Bang V V.
AU - Hannan, Anthony J J.
AU - Burrows, Emma L L.
N1 - Funding Information:
A.S is supported by an Australian Government Research Training Program Scholarship and Yulgilbar top-up scholarship. A.M.Z.J is supported by an Australian Government Research Training Program Scholarship A.J.H. is a National Health and Medical Research Council (NHMRC) Principal Research Fellow and has been supported by an Australian Research Council (ARC) FT3 Future Fellowship (FT100100835). E.L.B. is supported by a NHMRC-ARC Dementia Research Development Fellowship. C.T.O.N is supported by an Australian Research Council (ARC) Linkage grant (LP160100126) and a Melbourne Research Fellowship. This work was supported by directed research costs associated to a NHMRC-ARC Dementia Research Development fellowship.
Funding Information:
We would like to thank past and present laboratory members for useful discussions and technical assistance. We thank Britany Cuic, Maddison Ible, Daniel Drieberg, Shannon Currin Craig Thompson and Brett Purcell for their assistance in mouse husbandry and management of equipment. Thank you to Nippy's Ltd, for the donation of Ice Strawberry milk to our study. A.S is supported by an Australian Government Research Training Program Scholarship and Yulgilbar top-up scholarship. A.M.Z.J is supported by an Australian Government Research Training Program Scholarship A.J.H. is a National Health and Medical Research Council (NHMRC) Principal Research Fellow and has been supported by an Australian Research Council (ARC) FT3 Future Fellowship (FT100100835). E.L.B. is supported by a NHMRC-ARC Dementia Research Development Fellowship. C.T.O.N is supported by an Australian Research Council (ARC) Linkage grant (LP160100126) and a Melbourne Research Fellowship. J.K.H.L. is supported by the Guelma-Alaexander fellowship in Neuroscience and V.H.Y.W. are supported by an Australian Research Council (ARC) Linkage grant (LP160100126). This work was supported by directed research costs associated to a NHMRC-ARC Dementia Research Development fellowship. We would also like to acknowledge the operational infrastructure support from the State Government of Victoria.
Publisher Copyright:
© 2021 Elsevier Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1∆E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.
AB - Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1∆E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.
KW - APP/PS1
KW - Executive function
KW - Extinction
KW - Mice
KW - Rodent
KW - Touchscreen
KW - Visual discrimination
UR - http://www.scopus.com/inward/record.url?scp=85114684677&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2021.08.004
DO - 10.1016/j.neurobiolaging.2021.08.004
M3 - Article
C2 - 34509856
AN - SCOPUS:85114684677
SN - 0197-4580
VL - 108
SP - 58
EP - 71
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -