High Levels of <i>β</i>-Amyloid, Tau, and Phospho-Tau in Red Blood Cells as Biomarkers of Neuropathology in Senescence-Accelerated Mouse

Alzheimer's Disease (AD) is the most common Neurodegenerative Disease (ND), primarily characterised by neuroinflammation, neuronal plaques of <i>β</i>-amyloid (A<i>β</i>), and neurofibrillary tangles of hyperphosphorylated tau. <i>α</i>-Synuclein (<i>α</i>-syn) and its heteroaggregates with A<i>β</i> and tau have been recently included among the neuropathological elements of NDs. These pathological traits are not restricted to the brain, but they reach peripheral fluids as well. In this sense, Red Blood Cells (RBCs) are emerging as a good model to investigate the biochemical alterations of aging and NDs. Herein, the levels of homo- and heteroaggregates of ND-related proteins were analysed at different stages of disease progression. In particular, a validated animal model of AD, the SAMP8 (Senescence-Accelerated Mouse-Prone) and its control strain SAMR1 (Senescence-Accelerated Mouse-Resistant) were used in parallel experiments. The levels of the aforementioned proteins and of the inflammatory marker interleukin-1<i>β</i> (IL-1<i>β</i>) were examined in both brain and RBCs of SAMP8 and SAMR1 at 6 and 8 months. Brain A<i>β</i>, tau, and phospho-tau (p-tau) were higher in SAMP8 mice than in control mice and increased with AD progression. Similar accumulation kinetics were found in RBCs, even if slower. By contrast, <i>α</i>-syn and its heterocomplexes (<i>α</i>-syn-A<i>β</i> and <i>α</i>-syn-tau) displayed different accumulation kinetics between brain tissue and RBCs. Both brain and peripheral IL-1<i>β</i> levels were higher in SAMP8 mice, but increased sooner in RBCs, suggesting that inflammation might initiate at a peripheral level before affecting the brain. In conclusion, these results confirm RBCs as a valuable model for monitoring neurodegeneration, suggesting peripheral A<i>β</i>, tau, and p-tau as potential early biomarkers of AD.