Abstract
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 Aβ40, (all p < 0.05). SDP prevented these effects of aging and reduced Bace1 levels (all p < 0.05). Senescence increased the expression of Mme1 and Ide1 and pro-inflammatory cytokines (Il-17 and Il-18; all p < 0.05); these changes were prevented by SDP supplementation. Moreover, SDP increased Tgf-β expression (p < 0.05). Furthermore, in aged mice, the gene expression levels of the microglial activation markers Trem2, Ym1, and Arg1 were increased, and SDP prevented these increases (all p < 0.05). Thus, dietary SDP might delay AD onset by reducing its hallmarks in senescent mice.
Highlights
The prevalence of Alzheimer’s disease (AD), already the most common type of dementia, is increasing at an alarming rate due to the life expectancy improvements of recent decades [1]. This neurodegenerative disorder, which leads to cognitive decline, is characterized by aberrant amyloid precursor protein (APP) processing, the deposition of β-amyloid (Aβ) peptides such as Aβ40 and Aβ42, and the aggregation of hyperphosphorylated tau (p-tau) protein, all processes that are accompanied by neuronal loss [2]
Aβ peptides tend to self-aggregate as oligomers in β-amyloid or senile plaques, with extracellular Aβ accumulation caused by cleavage of APP by the β-secretase BACE1 [3]
Aging increased the abundance of sAPPβ in the brain tissue compared to young mice (p = 0.030; Figure 1B)
Summary
The prevalence of Alzheimer’s disease (AD), already the most common type of dementia, is increasing at an alarming rate due to the life expectancy improvements of recent decades [1] This neurodegenerative disorder, which leads to cognitive decline, is characterized by aberrant amyloid precursor protein (APP) processing, the deposition of β-amyloid (Aβ) peptides such as Aβ40 and Aβ42 , and the aggregation of hyperphosphorylated tau (p-tau) protein, all processes that are accompanied by neuronal loss [2]. GSK3β, in addition to its role in the pathogenesis of NFTs, promotes pro-inflammatory pathways through nuclear factor kappa B (NF-κB) activation It is inhibited when phosphorylated at Ser, which stimulates its glucose synthesis-related physiological effects [5]. CDK5 becomes hyperactive and causes aberrant hyperphosphorylation of tau proteins in NFTs [6] and interferes with the proteolytic processing of APP, modulating Aβ by affecting the secretases, which are critical for the hydrolysis of APP [7]
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