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Symptoms of cognitive decline were observed from initial LOAD stages, suggesting a continuous memory deterioration caused by subtle pathological alterations in the primary disease factors (for example, vascular/metabolic dysregulation and A effects). Our plasma and CSF results suggest the presence of early peripheral vascular alterations in the disease, and reveal new evidence about inflammatory activation, insulin resistance and associated lipid metabolism dysfunction. Finally, we highlight current limitations and challenges associated with the multifactorial modelling of LOAD.

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