Event Title
Effects of β-amyloid precursor protein (APP) plaques on working memory in knock-in mouse models of Alzheimer’s Disease
Abstract
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that accounts for the majority of dementia in the elderly. It is characterized by the deposition of β-amyloid (Aβ) precursor protein (APP) plaques throughout the brain, resulting in cognitive impairments. While AD is characterized by dementia, deficits in working memory (WM), the ability to hold information in the mind over a brief period, have a substantial impact on everyday functioning. However, the relationship between APP plaques and WM remains relatively obscure. We do not know whether Aβ deposition impacts WM function or if WM impairment due to normal aging can be slowed or reversed. Therefore, this project aims to characterize the relationship between APP plaques and WM using a novel knock-in (KI) mouse model of AD. WM performance in KI and littermate control (WT) mice was assessed using an automated touchscreen paradigm, called the Trial Unique Non-Matching-to-Location (TUNL) task. During TUNL, mice hold the location of a sample stimulus in WM over a delay period and use this information to correctly choose a novel location when it is presented together with the original sample. Across all delays, KI mice are consistently showing poorer performance compared with WT mice, indicating that Aβ plaques contribute to significant WM impairments. Future directions include treating the mice with the acetylcholinesterase inhibitor Donepezil to test whether the cognitive decline can be reversed. This research may open new avenues in investigating other facets of AD pathology and may also have downstream applications for therapeutic development.
Presentation Type
Oral Presentation
Effects of β-amyloid precursor protein (APP) plaques on working memory in knock-in mouse models of Alzheimer’s Disease
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that accounts for the majority of dementia in the elderly. It is characterized by the deposition of β-amyloid (Aβ) precursor protein (APP) plaques throughout the brain, resulting in cognitive impairments. While AD is characterized by dementia, deficits in working memory (WM), the ability to hold information in the mind over a brief period, have a substantial impact on everyday functioning. However, the relationship between APP plaques and WM remains relatively obscure. We do not know whether Aβ deposition impacts WM function or if WM impairment due to normal aging can be slowed or reversed. Therefore, this project aims to characterize the relationship between APP plaques and WM using a novel knock-in (KI) mouse model of AD. WM performance in KI and littermate control (WT) mice was assessed using an automated touchscreen paradigm, called the Trial Unique Non-Matching-to-Location (TUNL) task. During TUNL, mice hold the location of a sample stimulus in WM over a delay period and use this information to correctly choose a novel location when it is presented together with the original sample. Across all delays, KI mice are consistently showing poorer performance compared with WT mice, indicating that Aβ plaques contribute to significant WM impairments. Future directions include treating the mice with the acetylcholinesterase inhibitor Donepezil to test whether the cognitive decline can be reversed. This research may open new avenues in investigating other facets of AD pathology and may also have downstream applications for therapeutic development.