Behavioral and Neuronal Characterizations, across Ages, of the TgSwDI Mouse Model of Alzheimer's Disease

• Published in: Genes 2024-01, Vol.15 (1), p.47
• Main Authors: Tan, Natalie A, Carpio, Angelica M Alvarado, Heller, H Craig, Pittaras, Elsa C
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer's disease; Amyloid beta-Peptides - genetics; Analysis; Animals; Behavior; Brain; Brain research; Brain slice preparation; Cerebellum; Cognition; Cognitive ability; Cognitive Dysfunction; Disease Models, Animal; Experiments; Genetic engineering; Hippocampus; Humans; Immunohistochemistry; Infant; Laboratory animals; Memory; Mice; Neurodegenerative diseases; Neurofibrillary tangles; Neurons; Neurophysiology; Pattern recognition; Peptides; Plaque, Amyloid; Senile plaques; Short term memory; Spatial memory; Tau protein; Transgenic mice; β-Amyloid
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes15010047

Alzheimer's disease (AD) is a neurodegenerative disorder that currently affects as many as 50 million people worldwide. It is neurochemically characterized by an aggregation of β-amyloid plaques and tau neurofibrillary tangles that result in neuronal dysfunction, cognitive decline, and a progressive loss of brain function. TgSwDI is a well-studied transgenic mouse model of AD, but no longitudinal studies have been performed to characterize cognitive deficits or β-amyloid plaque accumulation for use as a baseline reference in future research. Thus, we use behavioral tests (T-Maze, Novel Object Recognition (NOR), Novel Object Location (NOL)) to study long-term and working memory, and immunostaining to study β-amyloid plaque deposits, as well as brain size, in hippocampal, cerebellum, and cortical slices in TgSwDI and wild-type (WT) mice at 3, 5, 8, and 12 months old. The behavioral results show that TgSwDI mice exhibit deficits in their long-term spatial memory starting at 8 months old and in long-term recognition memory at all ages, but no deficits in their working memory. Immunohistochemistry showed an exponential increase in β-amyloid plaque in the hippocampus and cortex of TgSwDI mice over time, whereas there was no significant accumulation of plaque in WT mice at any age. Staining showed a smaller hippocampus and cerebellum starting at 8 months old for the TgSwDI compared to WT mice. Our data show how TgSwDI mice differ from WT mice in their baseline levels of cognitive function and β-amyloid plaque load throughout their lives.