P3‐106: Acute Systemic Infection and FCΓ Receptors in Alzheimer’s Disease: An Immunosuppressive Environment

Abstract

training (AT) can enhance cognition and brain volume of regions sensitive to both aging and neurodegeneration. However, a large degree of variation exists in exercise efficacy on cognition and notably, women seem to show greater cognitive benefit from AT than men. However, few studies have examined this sex difference directly or comprehensively. Apolipoprotein E type 4 allele (APOE4) influences disease progression in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Importantly, cumulating evidence suggests that APOE4 interacts with sex in AD and possibly VCI to infer greater risk in women. Thus, we examined whether sex interacts with APOE status to moderate the efficacy of AT in older adults at risk for dementia. Methods: A single-blind RCT was conducted in older adults (n¼29 per sex) with subcortical VCI who engaged in 6-months of AT (3x/week) or usual care (control group). Here, we conduct secondary analysis of executive functioning measured at baseline and 6-months using: 1) Trail Making Test (TMT; set-shifting); 2) Digit Symbol Substitution Test (DSST; sustained-attention); 3) Stroop Test (selective-attention, conflict resolution). APOE genotype was determined using TaqMan assay. Participants were categorized as either APOE4+ or APOE-. Analysis of covariance was conducted separately for each executive test, controlling for baseline performance, global cognitive functioning, and age. Results: In the TMT, compared with controls AT significantly enhanced performance in APOE+ females and tended to enhance performance in APOE-females. Interestingly, AT had the opposite effect in males. Compared with controls, AT reduced performance on the TMT in APOE+ males and had no effect in APOE-males. Closer inspection indicated that 3 of the 5 APOE+ males showed large decrements in performance after exposure to the AT intervention. Performance on the DSST and Stroop were not significantly influenced by sex or APOE status. Conclusions: Although preliminary, due to the small sample size, our results are compelling and suggest that biological sex can interact with genotype to moderate exercise efficacy on brain health in older adults at high risk for progression to dementia.Background: Ageing is known as the main risk factor for Alzheimer's Disease (AD) which is characterised by the accumulation of Amyloid-beta (A-beta) in the brain. It remains unclear how agerelated-changes affect the amyloid precursor protein (APP), or A-beta directly, during ageing and increase the extracellular accumulation of A-beta in AD. Using different A-beta and APP specific antibodies, we investigated age-related changes in APP and A-beta, in post-mortem human brain provided by Brains for Dementia Research and BRAIN UK. Methods: Parietal cortex from 27 AD cases and cognitive normal controls, including 32 AD age-matched (OC, >65 years old) and 11 young (YC, <65 years old) cases, were immunostained for: a) APP and A-beta (clone 4G8), b) specifically A-beta (clone 82E1), c) specifically APP (clone 22C11). Quantification was performed by...