Affiliations: [a] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| [b] Department of Psychology, University of New Haven, New Haven, CT, USA
| [c] Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA
Correspondence:
[*]
Correspondence to: Farhan Ali, Department of Psychiatry, Yale University School of Medicine, 300 George St., Suite 901, New Haven, CT 06511, USA. Tel.: +1 203 785 6396; E-mail: [email protected].
Abstract: Alzheimer’s disease (AD) has several hallmark features including amyloid-β (Aβ) plaque deposits and neuronal loss. Here, we characterized Aβ plaque aggregation and parvalbumin-positive (PV) GABAergic neurons in 6–9-month-old 5xFAD mice harboring mutations associated with familial AD. We used immunofluorescence staining to compare three regions in the frontal cortex—prelimbic (PrL), cingulate (Cg, including Cg1 and Cg2), and secondary motor (M2) cortices—along with primary somatosensory (S1) cortex. We quantified the density of Aβ plaques, which showed significant laminar and regional vulnerability. There were more plaques of larger sizes in deep layers compared to superficial layers. Total plaque burden was higher in frontal regions compared to S1. We also found layer- and region-specific differences across genotype in the density of PV interneurons. PV neuron density was lower in 5xFAD mice than wild-type, particularly in deep layers of frontal regions, with Cg (–50%) and M2 (–39%) exhibiting the largest reduction. Using in vivo two-photon imaging, we longitudinally visualized the loss of frontal cortical PV neurons across four weeks in the AD mouse model. Overall, these results provide information about Aβ deposits and PV neuron density in a widely used mouse model for AD, implicating deep layers of frontal cortical regions as being especially vulnerable.
