Longitudinal Evaluation of the Detection Potential of Serum Oligoelements Cu, Se and Zn for the Diagnosis of Alzheimer’s Disease in the 3xTg-AD Animal Model

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of β-amyloid (Aβ) and hyperphosphorylated tau, leading to neuroinflammation, oxidative stress, and neuronal death. Early detection of AD remains a challenge, as clinical manifestations only emerge in the advanced stages, limiting therapeutic interventions. Minimally invasive biomarkers are essential for early identification and monitoring of disease progression. This study aims to evaluate the sensitivity of the relationship between serum oligoelement levels as biomarkers and the monitoring of AD progression in the 3xTg-AD model. Transgenic 3xTg-AD mice and C57BL/6 controls were evaluated over 12 months through serum oligoelement quantification using inductively coupled plasma mass spectrometry (ICP-MS), Aβ deposition via immunohistochemistry, and cognitive assessments using memory tests (Morris water maze and novel object recognition test), as well as spontaneous locomotion analysis using the open field test. The results demonstrated that oligoelements (copper, zinc, and selenium) were sensitive in detecting alterations in the AD group, preceding cognitive and motor deficits. Immunohistochemistry was performed for qualitative purposes, confirming the presence of β-amyloid in the CNS of transgenic animals. Up to the third month, labeling was moderate and restricted to neuronal cell bodies; from the fifth month onward, evident extracellular deposits emerged. Behavioral assessment indicated impairments in spatial and episodic memory, as well as altered locomotor patterns in AD mice. These findings reinforce that oligoelement variations may be associated with neurodegenerative processes, including oxidative stress and synaptic dysfunction. Thus, oligoelement analysis emerges as a promising approach for the early diagnosis of AD and the monitoring of disease progression, potentially contributing to the development of new therapeutic strategies.