Increasing evidence shows that cardiovascular diseases (CVDs) are associated with an increased risk of cognitive impairment and Alzheimer's diseases (AD). It is unknown whether systemic vascular dysfunction occurs prior to the development of AD, if this occurs in a sex-dependent manner, and whether …

Mice All mouse experiments were performed according to protocols approved by the Institutional Animal Care and Use Committees (IACUC) at Korea Advanced Institute of Science and Technology (KAIST) and the Institute for Basic Science (IBS), adhering strictly to ethical guidelines. B6.Cg-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax (APP/PS1) mice and B6.Cg-Tg(APPSwFlLon, PSEN1*M146L*L286V)6799Vas/Mmjax (5×FAD) mice were produced in our laboratory and maintained by breeding with C57BL/6J mice.

All mouse experiments were performed according to protocols approved by the Institutional Animal Care and Use Committees (IACUC) at Korea Advanced Institute of Science and Technology (KAIST) and the Institute for Basic Science (IBS), adhering strictly to ethical guidelines. B6.Cg-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax (APP/PS1) mice and B6.Cg-Tg(APPSwFlLon, PSEN1*M146L*L286V)6799Vas/Mmjax (5×FAD) mice were produced in our laboratory and maintained by breeding with C57BL/6J mice. Mice were housed under a 12 h–12 h light–dark cycle. Both male and female mice were used unless otherwise specified in the figure legends. All mice were randomly assigned to experiments, which were performed by investigators blinded to experimental conditions. Gender was not considered unless explicitly noted in figure legends. Human tissue sections Human formalin-fixed paraffin-embedded (FFPE) sections were provided by the SNUH Brain Bank and use of these sections for this study was reviewed and determined to be exempt from review by the Public Institutional Review Board designated by the Ministry of Health and Welfare, Republic of Korea. All procedures involving human-derived materials were conducted in accordance with relevant regulations. Cell lines HEK293T cells (ATCC) were used solely for AAV production. Cells were maintained in our laboratory and were not independently authenticated for this study. HEK293T cells were confirmed...

Read the full paper: M1 muscarinic receptor modulation drives sex-specific alterations of Alzheimer’s pathophysiology in APPswe/PSEN1ΔE9 Mice

Littermates of female C57BL/6 wild-type (WT) and APPswe/PS1dE9 transgenic (Tg) mice (The Jackson Laboratory, Bar Harbor, USA) were maintained as a colony at the University of Otago, Hercus Taieri Research Unit. Animals were group-housed in individually ventilated cages until vector delivery by tail-vein injection at 6 months of age, after which they were single-housed until euthanised at 9–10 months of age. Food and water were available ad libitum, and the cage contained one red plastic tube and shredded wood bedding as per standard housing. Animals were kept on a 12-h light: dark cycle (7 am–7 pm), and the room temperature was controlled via a thermostat set at 21 °C. All animal use was compliant with New Zealand’s Animal Welfare Act 1991 and all procedures were approved by the University of Otago Animal Ethics Committee (approval code #19/90). Animals were randomly assigned at the time of the tail vein injection into designated groups based on treatment and genotype. All experiments and analyses were carried out in a blinded manner. After virus injection, mice were weighed every week and assessed for any physical or behavioural abnormalities for the duration of the experiment. Adeno-associated viral vectors (AAV) Approval for the generation and use...

Although evidence of dysregulation in central serotonergic signalling is widespread in Alzheimer's d

Extracellular beta-amyloid (A{beta}) is thought to cause impairments in brain wide functional connec