| First Author | Arezoumandan S | Year | 2021 |
| Journal | Neurosci Lett | Volume | 758 |
| Pages | 136010 | PubMed ID | 34090937 |
| Mgi Jnum | J:368195 | Mgi Id | MGI:6825342 |
| Doi | 10.1016/j.neulet.2021.136010 | Citation | Arezoumandan S, et al. (2021) Hippocampal neurobiology and function in an aged mouse model of TDP-43 proteinopathy in an APP/PSEN1 background. Neurosci Lett 758:136010 |
| abstractText | Aging is a major risk factor for Alzheimer's disease (AD), the most common cause of dementia worldwide. TDP-43 proteinopathy is reported to be associated with AD pathology is almost 50% of cases. Our exploratory study examined near end-stage (28 months old) mice selectively driving expression of human TDP-43 in the hippocampus and cortex in an APP/PSEN1 background. We hypothesized that hippocampal neuropathology caused by beta-amyloidosis with TDP-43 proteinopathy induced in this model, resembling the pathology seen in AD cases, manifest with changes in resting state functional connectivity. In vivo magnetic resonance imaging and post-mortem histology were performed on four genotypes: wild type, APP/PSEN1, Camk2a/TDP-43, and Camk2a/TDP-43/APP/PSEN1. Our results revealed loss of functional coupling in hippocampus and amygdala that was associated with severe neuronal loss in dentate gyrus of Camk2a/TDP-43/APP/PSEN1 mice compared to APP/PSEN1 and wild type mice. The loss of cells was accompanied by high background of beta-amyloid plaques with sparse phosphorylated TDP-43 pathology. The survival rate was also reduced in Camk2a/TDP-43/APP/PSEN1 mice compared to other groups. This end-of-life study provides exploratory data to reach a better understanding of the role of TDP-43 hippocampal neuropathology in diseases with co-pathologies of TDP-43 proteinopathy and beta-amyloidosis such as AD and limbic predominant age-related TDP-43 encephalopathy (LATE). |
