High fat/low carbohydrate diet is associated with increased solubilizable Aβ42 levels in a murine model of aggressive AD neuropathology. TgCRND8 mice (n = 51) were fed for 14 weeks with regular commercial chow (RC), high fat custom chow (HF), high protein custom chow (HP), or high carbohydrate custom chow (HC). [N.B., diet groups are named by either major component only (HF, HP, HC) or by an abbreviation indicating both major and minor components (HF/LC, HP/LC, HC/LF); HF or HF/LC = high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); HP or HP/LC = high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); HC or HC/LF = high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat)]. At the end of this period, brains were harvested, and levels of Aβ42 were evaluated as described in Methods. Statistical significance (p = 0.014) was determined by pairwise comparison to RC. Data represent means ± S.D.