5xfad

APP^NL-G-F mice were obtained from the RIKEN Center for Brain Science, Wako, Japan [25 (link)]. 5xFAD and Tg-APPsw/PSEN1DE9 (PA) mice were purchased from Jackson Laboratory (stock # 34840 and 004462, respectively). All mice in the study were maintained and used according to protocols approved by the Institutional Animal Care and Use Committee of the University of Connecticut. AD postmortem brain samples were obtained from the NIH NeuroBioBank (Harvard Brain Tissue Resource Center; Human Brain and spinal Fluid Resource Center, Los Angeles; Mount Sinai NBTR Tissue Distribution; University of Maryland Brain and Tissue Bank; University of Miami Brain Endowment Bank).

Mice co-expressing five familial Alzheimer’s disease mutations (5xFAD) were purchased from Jackson Laboratories (Bar Harbor, ME, USA; [25 (link)]) on the C57BL/6J background and were mated with CB₂^EGFP/f/f and CB₂^−/− mice and backcrossed for at least five generations to generate CB₂^EGFP/f/f/5xFAD and CB₂^−/−/5xFAD mice. Animals employed in the present experiments were 3 to 6 months old; this period was chosen based on previously published data [25 (link), 36 (link)] in order to allow for the appearance of amyloid deposits.

Foxo3^fl/fl (Paik et al., 2007 (link)), Nestin‐Cre (Tronche et al., 1999 (link)), Aldh1l1‐CreER (Srinivasan et al., 2016 (link)), and 5xFAD (Oakley et al., 2006 (link)) mouse lines were obtained from the Jackson Laboratories. The aged C57BL/6J mice were obtained from the aging rodent colony of the National Institute on Aging. The sample size was determined based on previous studies (Lian et al., 2016 (link)). Both male and female mice were used, and these are specified in the results and figure legends. Investigators were blinded to the group identities during data collection and analysis. For AAV injections, postnatal day 3 pups were anesthetized via hypothermia and injected i.c.v. free‐hand with 2.5 × 10¹⁰ viral particles per side using a 28‐gauge needle attached to a Hamilton syringe as described previously (Chen et al., 2021 (link); Martini‐Stoica et al., 2018 (link)). RNA sequencing of total RNA was performed using the Illumina platform. Untargeted lipidomics was carried using a Vanquish UPLC and a Lumos orbitrap mass spectrometer (Thermo Fisher Scientific). The detailed methods for these experiments and other standard procedures including qPCR, Western blotting, immunofluorescence staining and associated image acquisition and analysis are provided in Supplementary Information.

Alzheimer’s disease model mice, 5XFAD (The Jackson Laboratory, Bar Harbor, ME; stock no. 006554, Tg6799), were used for western blot and DAB staining and maintained in Seoul National University’s mouse facility. The mice express the human amyloid precursor protein bearing the Swedish (K670N, M671L), Florida (I716V), and London (V717I) mutations and two human presenilin-1 mutations (M146L, L286V). All animal experiments were performed in accordance with the Principle of Laboratory Animal Care (NIH publication No. 85–23, revised 1985) and the Animal Care and Use Guidelines of Seoul National University, Seoul, Korea. All experimental protocols were approved by Institutional Animal Care and Use Committee (IACUC) in Seoul National University Hospital.

All animal experiments were carried out in accordance with the Guidelines for the Care and Use of Laboratory Animals of the Sugitani Campus of the University of Toyama. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama. The approval number for the animal experiments is A2014INM-1, and the confirmation number for the recombinant gene experiments is G2013INM-1.
Transgenic mice (5XFAD) were obtained from Jackson Laboratory (Bar Harbor, ME, United States). They were maintained as double hemizygotes by crossing with B6/SJL F1 breeders. To test the effect of the DR extract on 5XFAD mice, we used 5XFAD mice (male and female, 6–8 months old) and non-transgenic wild-type littermate mice (male and female, 6–8 months old). To investigate the effect of naringenin on 5XFAD mice, we used 5XFAD mice (male, 8–12 months old) and non-transgenic wild-type littermate mice (male, 8–12 months old). All mice were housed with free access to food and water and were kept in a controlled environment (25 ± 2°C, 12-h light/dark cycle starting at 7:00 am).