Experimental animals
All of the procedures in this study were carried out in accordance with
the British Home Office regulations under the Animal Scientific
Procedure Act 1986, under the project licence PPL: P1ADA633A held by the
principal investigator, Dr. Afia Ali. All procedures were approved by
both internal and external UCL ethics committees, and in accordance with
the ARRIVE guide-lines for reporting experiments involving animals
(McGrath et al., 2010). A total of ~100 animals (disease
model and wild-type) were used in this study. The animals hadad-libitum access to food and water and were reared in cages of
maximum 5 inhabitants, with a day: night cycle of 12 hours: 12 hours.
The knock-in APPNL-F/NL-F AD mouse model was
used for experiments (Saito et al., 2014), which consists of the
introduction of two familial AD (FAD) mutations: KM670/671NL and I716F.
The former, identified as the Swedish mutation, increases β-site
cleavage of APP to produce elevated amounts of both Aβ40and Aβ42, whereas the latter, known as the
Beyreuther/Iberian mutation, promotes γ-site cleavage at C-terminal
position 42, thereby increasing the
Aβ42/Aβ40 ratio in favour of the more
hydrophobic Aβ42 (Saito et al., 2014). Both features are
key to the integrity of the disease phenotype. The knock-in line was
crossed with C57BL/6 mice, and maleAPPNL-F/NL-F and age-matched wild-type
(C57BL/6) mice from the same breeding were used as control at 9 - 18
months.
Animals were genotyped via standard polymerase chain reaction using the
following four primers: 5′-ATCTCGGAAGTGAAGATG-3′,
5′-TGTAGATGAGAACTTAAC-3′, 5′-ATCTCGGAAGTGAATCTA-3′, and
5′-CGTATAATGTATGCTATACGAAG-3′ as previously described (Saito et al.,
2014). Further details of rationale for selecting this mouse model can
be found in Petrache et al., (2019).