Abstract
Alzheimer's Disease (AD) is the most common Neurodegenerative Disease (ND), primarily characterised by neuroinflammation, neuronal plaques of β-amyloid (Aβ), and neurofibrillary tangles of hyperphosphorylated tau. α-Synuclein (α-syn) and its heteroaggregates with Aβ 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-1β (IL-1β) were examined in both brain and RBCs of SAMP8 and SAMR1 at 6 and 8 months. Brain Aβ, 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, α-syn and its heterocomplexes (α-syn-Aβ and α-syn-tau) displayed different accumulation kinetics between brain tissue and RBCs. Both brain and peripheral IL-1β 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 Aβ, tau, and p-tau as potential early biomarkers of AD.
Highlights
Alzheimer’s Disease (AD) is the most common form of Neurodegenerative Disease (ND) and the leading cause of dementia in the elderly population
The presence and quantification of total β-Amyloid p-tau (Aβ), tau, and α-syn and its heterocomplexes (α-synAβ and α-syn-tau) in Red Blood Cells (RBCs) and in brain tissues were assessed by a “homemade” sandwich enzyme-linked immunosorbent assay (ELISA) system [11, 33, 34]
SAMP8 mice at 4, 6, and 8 months displayed a significant increase in escape latency time at every test day compared with Senescence-accelerated mouse-resistant IL-1β (SAMR1) mice (Figure 2(a))
Summary
Alzheimer’s Disease (AD) is the most common form of Neurodegenerative Disease (ND) and the leading cause of dementia in the elderly population. The molecular hallmarks associated with AD are primarily represented by misfolding and brain deposition of β-amyloid protein 1-42 (Aβ), which generates the amyloid plaques, and by neurofibrillary tangles (NTs) of hyperphosphorylated tau protein. According to the “amyloid hypothesis,” Aβ promotes a glycogen synthase kinase-mediated tau phosphorylation, resulting in amyloid plaques and NTs, which damage the blood-brain barrier and produce neuronal apoptosis, inflammation, and oxidative stress [1]. It has been suggested that neuroinflammation in AD, at its earlier stages, reflects a vicious cycle of microglial activation, release of proinflammatory factors, and neuronal damage [2, 3]. Besides amyloid plaques and NTs, the disease has been
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