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Age-dependent vulnerability to spatial memory interference in APP/PS1 mice.

Dejana Mitrovic Tartanoglu^1,2, Can Hicabi Tartanoglu^1,2, Charlotte Sonnenberg^1,2

¹German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.

Frontiers in Aging Neuroscience

|June 18, 2026

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Alzheimer

Area of Science:

Neuroscience
Cognitive Science
Animal Models of Disease

Background:

Alzheimer's disease (AD) is characterized by memory loss, but the impact of amyloid pathology on spatial memory updating remains unclear.
Investigating how amyloidosis affects the flexible updating of competing spatial representations is crucial for understanding AD.
The Objects in Updated Locations (OUL) paradigm offers a novel approach to study these deficits in mouse models.

Purpose of the Study:

To investigate the effects of amyloidosis on spatial memory updating and the handling of competing mnemonic information.
To assess spatial memory flexibility and interference in APP/PS1 mice using the OUL paradigm.
To correlate behavioral performance with neuronal activity in key brain regions.

Main Methods:

Keywords:

APP/PS1 AD mice Alzheimer’s disease aging behavior c-Fos hippocampus memory updating spatial memory

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APP/PS1 and wild-type mice were tested using the OUL paradigm to assess object displacement and spatial updating.

Automated behavioral tracking quantified exploration, while cFos immunohistochemistry measured neuronal recruitment.

Performance was evaluated during object displacement and subsequent updating sessions with competing spatial information.

Main Results:

APP/PS1 mice showed impaired discrimination of displaced objects and weaker performance in updating overlapping spatial representations compared to controls.
Deficits in APP/PS1 mice were exacerbated under conditions of competing spatial information and increased with age.
Neuronal activity in hippocampal regions correlated with performance in control mice but not in APP/PS1 mice.

Conclusions:

Amyloidosis impairs spatial memory reliability and the ability to handle competing spatial information, particularly during flexible updating.
Age-related vulnerability to interference-related spatial memory deficits is suggested.
The OUL paradigm is a valuable tool for studying memory updating impairments in Alzheimer's disease pathology.