Anxiety and Alzheimer’s disease: Behavioral analysis and neural basis in rodent models of Alzheimer’s-related neuropathology

• Published in: Neuroscience and biobehavioral reviews Vol. 127; pp. 647 - 658
• Main Authors: Pentkowski, Nathan S., Rogge-Obando, Kimberly K., Donaldson, Tia N., Bouquin, Samuel J., Clark, Benjamin J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.08.2021
• Subjects: Alzheimer’s disease; Anxiety; Elevated plus-maze; light/dark test; Open field; Stress; Ventral hippocampus; APP; AD; EPM; Alzheimer’s disease; light/dark test; PFC; Open field; Stress; vHC; Ventral hippocampus; BNST; MCI; CRF; PAG; Anxiety; OFT; Elevated plus-maze; LDT; dHC; MBT; SIT; elevated plus-maze; anxiety; stress; open field; ventral hippocampus
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2021.05.005

•Human Alzheimer’s patients exhibit anxiety at the mild cognitive impairment stage of the disease, which is associated with an increased likelihood of developing dementia.•Transgenic rodent models of Alzheimer’s disease exhibit inconsistent markers of anxiety.•We suggest that future research will benefit from using a battery of tests to examine anxiety-like and emotional behavior in transgenic AD models. Alzheimer’s disease (AD) pathology is commonly associated with cognitive decline but is also composed of neuropsychiatric symptoms including psychological distress and alterations in mood, including anxiety and depression. Emotional dysfunction in AD is frequently modeled using tests of anxiety-like behavior in transgenic rodents. These tests often include the elevated plus-maze, light/dark test and open field test. In this review, we describe prototypical behavioral paradigms used to examine emotional dysfunction in transgenic models of AD, specifically anxiety-like behavior. Next, we summarize the results of studies examining anxiety-like behavior in transgenic rodents, noting that the behavioral outcomes using these paradigms have produced inconsistent results. We suggest that future research will benefit from using a battery of tests to examine emotional behavior in transgenic AD models. We conclude by discussing putative, overlapping neurobiological mechanisms underlying AD-related neuropathology, stress and anxiety-like behavior reported in AD models.