Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 72, Issue 4, Pages 1323-1339Publisher
IOS PRESS
DOI: 10.3233/JAD-181190
Keywords
5xFAD; amyloid-beta; cingulate cortex; familial Alzheimer's disease; frontal cortex; parvalbumin-positive neurons; plaques; secondary motor cortex
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Funding
- National Institute of Mental Health grant [R01MH112750]
- National Institute on Aging grant [P50AG047270]
- Alzheimer's Association Research Fellowship [AARF-17-504924]
- James Hudson Brown-Alexander Brown Coxe Postdoctoral Fellowship
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Alzheimer's disease (AD) has several hallmark features including amyloid-beta (A beta) plaque deposits and neuronal loss. Here, we characterized A beta plaque aggregation and parvalbumin-positive (PV) GABAergic neurons in 6-9-month-old 5xFADmice 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 A beta 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 A beta deposits and PV neuron density in a widely used mouse model for AD, implicating deep layers of frontal cortical regions as being especially vulnerable.
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