Dataset Information

Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (A?) and neurofibrillary tangles that usually begins 15-30 years before clinical diagnosis. Rodent models that recapitulate aggressive A? and/or the pathology of neurofibrillary tangles are essential for AD research. Accordingly, non-invasive early detection systems in these animal models are required to evaluate the phenotypic changes, elucidate the mechanism of disease progression, and facilitate development of novel therapeutic approaches. Although many behavioral tests efficiently reveal cognitive impairments at the later stage of the disease in AD models, it has been challenging to detect such impairments at the early stage. To address this issue, we subjected 4-6-month-old male AppNL-G-F/NL-G-F knock-in (App-KI) mice to touchscreen-based location discrimination (LD), different object-location paired-associate learning (dPAL), and reversal learning tests, and compared the results with those of the classical Morris water maze test. These tests are mainly dependent on the brain regions prone to A? accumulation at the earliest stages of the disease. At 4-6 months, considered to represent the early stage of disease when mice exhibit initial deposition of A? and slight gliosis, the classical Morris water maze test revealed no difference between groups, whereas touchscreen-based LD and dPAL tasks revealed significant impairments in task performance. Our report is the first to confirm that a systematic touchscreen-based behavioral test battery can sensitively detect the early stage of cognitive decline in an AD-linked App-KI mouse model. This system could be applied in future translational research.

SUBMITTER: Saifullah MAB

PROVIDER: S-EPMC7664057 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease.

Saifullah Md Ali Bin MAB Komine Okiru O Dong Yutao Y Fukumoto Kazuya K Sobue Akira A Endo Fumito F Saito Takashi T Saido Takaomi C TC Yamanaka Koji K Mizoguchi Hiroyuki H

Molecular brain 20201113 1

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (Aβ) and neurofibrillary tangles that usually begins 15-30 years before clinical diagnosis. Rodent models that recapitulate aggressive Aβ and/or the pathology of neurofibrillary tangles are essential for AD research. Accordingly, non-invasive early detection systems in these animal models are required to evaluate the phenotypic changes, elucidate the mechanism ...[more]

PMID: 33183323

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Project description:BackgroundIt has been proposed that children with Specific Language Impairment (SLI) have a selective deficit in procedural learning, with relatively spared declarative learning. In previous studies we and others confirmed deficits in procedural learning of sequences, using both verbal and nonverbal materials. Here we studied the same children using a task that implicates the declarative system, auditory-visual paired associate learning. There were parallel tasks for verbal materials (vocabulary learning) and nonverbal materials (meaningless patterns and sounds).MethodsParticipants were 28 children with SLI aged 7-11 years, 28 younger typically-developing children matched for raw scores on a test of receptive grammar, and 20 typically-developing children matched on chronological age. Children were given four sessions of paired-associate training using a computer game adopting an errorless learning procedure, during which they had to select a picture from an array of four to match a heard stimulus. In each session they did both vocabulary training, where the items were eight names and pictures of rare animals, and nonverbal training, where stimuli were eight visual patterns paired with complex nonverbal sounds. A total of 96 trials of each type was presented over four days.ResultsIn all groups, accuracy improved across the four sessions for both types of material. For the vocabulary task, the age-matched control group outperformed the other two groups in the starting level of performance, whereas for the nonverbal paired-associate task, there were no reliable differences between groups. In both tasks, rate of learning was comparable for all three groups.ConclusionsThese results are consistent with the Procedural Deficit Hypothesis of SLI, in finding spared declarative learning on a nonverbal auditory-visual paired associate task. On the verbal version of the task, the SLI group had a deficit in learning relative to age-matched controls, which was evident on the first block in the first session. However, the subsequent rate of learning was consistent across all three groups. Problems in vocabulary learning in SLI could reflect the procedural demands of remembering novel phonological strings; declarative learning of crossmodal links between auditory and visual information appears to be intact.

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Dataset Information

Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease.

Publications

Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease.

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