Patterns of cognitive decline and somatosensory processing in a mouse model of amyloid accumulation

Abstract

Pain and cognitive decline increase with age. In particular, there is a troubling relationship between dementia and pain, with some studies showing higher prevalence and inadequate treatment of pain in this population. Alzheimer's disease (AD) is one of the most common causes of dementia in older adults. Amyloid plaques are a hallmark of AD. The downstream processes these plaques promote are believed to affect neuronal and glial health and activity. There is a need to better understand how the neuropathological changes of AD shape neural activity and pain sensitivity. Here, we use the 5XFAD mouse model, in which dense amyloid accumulations occur at early ages, and in which previous studies reported signs of cognitive decline. We hypothesized that 5XFAD mice develop sensory and pain processing dysfunctions. Although amyloid burden was high throughout the brain, including in regions involved with sensory processing, we identified no functionally significant differences in reflexive or spontaneous signs of pain. Furthermore, expected signs of cognitive decline were modest; a finding consistent with variable results in the literature. These data suggest that models recapitulating other pathological features of Alzheimer's disease might be better suited to studying differences in pain perception in this disease. © 2021