| Summary: | Alzheimer’s disease (AD) is characterized by the aberrant processing of amyloid precursor protein (APP) and the accumulation of hyperphosphorylated tau, both of which are accompanied by neuroinflammation. Dietary supplementation with spray-dried porcine plasma (SDP) has anti-inflammatory effects in inflammation models. We investigated whether dietary supplementation with SDP prevents the neuropathological features of AD. The experiments were performed in 2- and 6-month-old SAMP8 mice fed a control diet, or a diet supplemented with 8% SDP, for 4 months. AD brain molecular markers were determined by Western blot and real-time PCR. Senescent mice showed reduced levels of p-GSK3β (Ser9) and an increase in p-CDK5, p-tau (Ser396), sAPPβ, and the concentration of Aβ<sub>40,</sub> (all <i>p</i> < 0.05). SDP prevented these effects of aging and reduced <i>Bace1</i> levels (all <i>p</i> < 0.05). Senescence increased the expression of <i>Mme1</i> and <i>Ide1</i> and pro-inflammatory cytokines (<i>Il-17</i> and <i>Il-18</i>; all <i>p</i> < 0.05); these changes were prevented by SDP supplementation. Moreover, SDP increased <i>Tgf-β</i> expression (<i>p</i> < 0.05). Furthermore, in aged mice, the gene expression levels of the microglial activation markers <i>Trem2</i>, <i>Ym1</i>, and <i>Arg1</i> were increased, and SDP prevented these increases (all <i>p</i> < 0.05). Thus, dietary SDP might delay AD onset by reducing its hallmarks in senescent mice.
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