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Background

Alzheimer’s disease (AD) remains as a silent and increasing threat to public health. More than 200 clinical trials for AD have ended with disappointing results and basically empty-handed. The amyloid hypothesis as a primary culprit of AD still centralises most of the efforts in the academic and private sectors, but we need to start to explore alternative avenues for early diagnosis and development of effective therapeutic approaches to treat or slow down the progression of neurodegeneration.

Biomarkers and neuroimaging

Diagnosis of AD usually occurs when the symptoms of mental decline are evident. Unfortunately, AD is a progressive neurodegenerative disorder from which there is no return once neuronal damage starts. The desperate need for effective biomarkers for AD have driven the exploration of genomic, metabolomic and proteomic markers in blood, cerebrospinal fluid (CSF) and tissue samples. Genetic biomarkers strongly implicated in early-onset AD include amyloid-β precursor protein  (AβPP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2), whereas apolipoprotein E-ε4 (APOE-ε4), bridging integrator 1 (BIN1), clusterin (CLU), phosphatidylinositol binding clathrin assembly lymphoid-myeloid (PICALM) and complement receptor 1 are connected with late-onset AD. Blood-derived biomarkers potentially correlated with AD include proteins: ceruloplasmin, complement factor H, serum amyloid P-complement precursor …