Amyloid precursor protein (APP) is closely associated with Alzheimer's disease (AD), and the accumulation of β-amyloid protein (Aβ) derived from its proteolytic cleavage in the brain is a key factor in the pathogenesis of AD. Using ES cell targeting technology, SMOC partially replaced the mouse App gene with the human APPNL-G-F sequence, enabling the expression of a human-mouse chimeric APPNL-G-F protein. In these homozygous mice, significant plaque accumulation gradually develops in the brain with increasing age.
Fig1. Detection of APP expression in brain by RT-PCR.
Fig2. (A) β-Amyloid (6E10) staining of WT and hAPPNL-G-F mice at 1, 3 and 6 months (magnification, 40x and 100x). (B) Statistics of 6E10 positive plaque area.
Fig3. (A) Thioflavine S staining of WT and hAPPNL-G-F mice at 1, 3 and 6 months (magnification, 40x and 100x). (B) Statistics of ThiS positive plaque area.
Mutations: APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V
Fig 1. Expression of Aβ in brain of 6-month-old 5xFAD mice.
Fig 2. ELISA analysis of CSF sample collected from 5xFAD mice for human Aβ42.
Fig 3. Results of Aβ 6E10 and Iba1 immunocostaining in 5xFAD mice after 3 months of Lecanemab treatment (90mpk, Q2W; n=6, male; dosing started at 7w).
Fig 4. Aβ 6E10 Area fraction in cortex and hippocampis of 5xFAD mice after Lecanemab treatment.
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