Longitudinal Assessment of Cognitive Function in the APPswe/PS1dE9 Mouse Model of Alzheimer's-related Beta-amyloidosis

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2023 Apr 29

PMID 37120419

Authors

Paul L Soto

Michael E Young

Giuliana M DiMarco

Brianna George

Tatiana Melnikova

Alena V Savonenko

Breanna N Harris

Affiliations

Soon will be listed here.

Abstract

Preclinical models of Alzheimer's disease (AD)-related cognitive decline can be useful for developing therapeutics. The current study longitudinally assessed short-term memory, using a delayed matching-to-position (DMTP) task, and attention, using a 3-choice serial reaction time (3CSRT) task, from approximately 18 weeks of age through death or 72 weeks of age in APPswe/PS1dE9 mice, a widely used mouse model of AD-related amyloidosis. Both transgenic (Tg) and non-Tg mice exhibited improvements in DMTP accuracy over time. Breaks in testing reduced DMTP accuracy but accuracy values quickly recovered in both Tg and non-Tg mice. Both Tg and non-Tg mice exhibited high accuracy in the 3CSRT task with breaks in testing briefly reducing accuracy values equivalently in the 2 genotypes. The current results raise the possibility that deficits in Tg APPswe/PS1dE9 mice involve impairments in learning rather than declines in established performances. A better understanding of the factors that determine whether deficits develop will be useful for designing evaluations of potential pharmacotherapeutics and may reveal interventions for clinical application.

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References

Jutten R, Grandoit E, Foldi N, Sikkes S, Jones R, Choi S . Lower practice effects as a marker of cognitive performance and dementia risk: A literature review. Alzheimers Dement (Amst). 2020; 12(1):e12055. PMC: 7346865. DOI: 10.1002/dad2.12055. View

Dodart J, Meziane H, Mathis C, Bales K, Paul S, Ungerer A . Behavioral disturbances in transgenic mice overexpressing the V717F beta-amyloid precursor protein. Behav Neurosci. 1999; 113(5):982-90. DOI: 10.1037//0735-7044.113.5.982. View

Borchelt D, Ratovitski T, Van Lare J, Lee M, Gonzales V, Jenkins N . Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 1997; 19(4):939-45. DOI: 10.1016/s0896-6273(00)80974-5. View

Perry R, Watson P, Hodges J . The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer's disease: relationship to episodic and semantic memory impairment. Neuropsychologia. 2000; 38(3):252-71. DOI: 10.1016/s0028-3932(99)00079-2. View

Wilson R, Segawa E, Boyle P, Anagnos S, Hizel L, Bennett D . The natural history of cognitive decline in Alzheimer's disease. Psychol Aging. 2012; 27(4):1008-17. PMC: 3534850. DOI: 10.1037/a0029857. View

Westerman M, Mariash A, Kotilinek L, Kawarabayashi T, Younkin L, Carlson G . The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci. 2002; 22(5):1858-67. PMC: 6758862. View

Amitai N, Markou A . Comparative effects of different test day challenges on performance in the 5-choice serial reaction time task. Behav Neurosci. 2011; 125(5):764-74. PMC: 3187548. DOI: 10.1037/a0024722. View

Wang L, Cao M, Pu T, Huang H, Marshall C, Xiao M . Enriched Physical Environment Attenuates Spatial and Social Memory Impairments of Aged Socially Isolated Mice. Int J Neuropsychopharmacol. 2018; 21(12):1114-1127. PMC: 6276026. DOI: 10.1093/ijnp/pyy084. View

Swainson R, Hodges J, Galton C, Semple J, Michael A, Dunn B . Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks. Dement Geriatr Cogn Disord. 2001; 12(4):265-80. DOI: 10.1159/000051269. View

10.

Lee A, Rahman S, Hodges J, Sahakian B, Graham K . Associative and recognition memory for novel objects in dementia: implications for diagnosis. Eur J Neurosci. 2003; 18(6):1660-70. DOI: 10.1046/j.1460-9568.2003.02883.x. View

11.

Cao M, Hu P, Zhang Y, Yan Y, Shields C, Zhang Y . Enriched physical environment reverses spatial cognitive impairment of socially isolated APPswe/PS1dE9 transgenic mice before amyloidosis onset. CNS Neurosci Ther. 2017; 24(3):202-211. PMC: 6490083. DOI: 10.1111/cns.12790. View

12.

Janus C, Pearson J, McLaurin J, Mathews P, Jiang Y, Schmidt S . A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature. 2001; 408(6815):979-82. DOI: 10.1038/35050110. View

13.

Watanabe T, Yamagata N, Takasaki K, Sano K, Hayakawa K, Katsurabayashi S . Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease. Brain Res. 2008; 1249:222-8. DOI: 10.1016/j.brainres.2008.10.029. View

14.

Lagadec S, Rotureau L, Hemar A, Macrez N, Delcasso S, Jeantet Y . Early temporal short-term memory deficits in double transgenic APP/PS1 mice. Neurobiol Aging. 2010; 33(1):203.e1-11. DOI: 10.1016/j.neurobiolaging.2010.07.023. View

15.

Cao D, Lu H, Lewis T, Li L . Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem. 2007; 282(50):36275-82. DOI: 10.1074/jbc.M703561200. View

16.

Robbins T . The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl). 2002; 163(3-4):362-80. DOI: 10.1007/s00213-002-1154-7. View

17.

Arendash G, King D, Gordon M, Morgan D, Hatcher J, Hope C . Progressive, age-related behavioral impairments in transgenic mice carrying both mutant amyloid precursor protein and presenilin-1 transgenes. Brain Res. 2001; 891(1-2):42-53. DOI: 10.1016/s0006-8993(00)03186-3. View

18.

Fowler K, Saling M, Conway E, Semple J, Louis W . Computerized neuropsychological tests in the early detection of dementia: prospective findings. J Int Neuropsychol Soc. 1997; 3(2):139-46. View

19.

Guo H, Cheng Y, Wu J, Wang C, Wang H, Zhang C . Donepezil improves learning and memory deficits in APP/PS1 mice by inhibition of microglial activation. Neuroscience. 2015; 290:530-42. DOI: 10.1016/j.neuroscience.2015.01.058. View

20.

Higgins G, Breysse N . Rodent model of attention: the 5-choice serial reaction time task. Curr Protoc Pharmacol. 2012; Chapter 5:Unit5.49. DOI: 10.1002/0471141755.ph0549s41. View