Longitudinal characterization reveals behavioral impairments in aged APP knock in mouse models

Area of Science:

• Neuroscience
• Genetics
• Pathology

Background:

• Amyloid beta (Aβ) pathology is central to Alzheimer's disease (AD).
• Previous mouse models often used overexpression systems with limitations.
• APP knock-in (KI) models offer a more refined approach to studying Aβ pathology.

Purpose of the Study:

• To characterize the onset of cognitive and motor deficits in APP knock-in (KI) mouse models.
• To establish a developmental timeline for behavioral impairments in APP^SAA and APP^WT mice.
• To provide a foundation for future research utilizing these AD models.

Main Methods:

• Longitudinal study over 16 months in APP^SAA and APP^WT KI mice.
• Assessment of cognitive functions, specifically spatial memory.
• Evaluation of motor function across different age points.
• Comparison between genetically modified (APP^SAA) and control (APP^WT) groups.

Main Results:

• No cognitive deficits were observed in either genotype during the first year of life.
• APP^SAA mice exhibited initial spatial memory decline at 16 months of age.
• Both APP^SAA and APP^WT mice showed impaired motor function at 16 months.
• APP^WT mice did not display cognitive deficits at 16 months.

Conclusions:

• APP^SAA KI mice develop behavioral impairments, including spatial memory deficits, starting around 16 months.
• Motor function deficits appear in both APP^SAA and APP^WT mice at 16 months.
• This study defines a critical age window for observing AD-related behavioral changes in these specific APP KI mouse models.