Taking these 15 proteins forward to the validation cohort (Cohort 2), 9 markers (total apoE (which refers to the APOE protein where the peptide is taken from a conserved region of ApoE and quantitate irrespective of isoform status), β-amyloid40, Carnosine Dipeptidase 1, cystatin C, insulin-like growth factor-binding protein 2, MDH, osteopontin, triggering receptor expressed on myeloid cells 2 and YKL-40) were significantly elevated in the patients with both clinically and neurochemically defined AD. This evidence concerns the gene TREM2 and Alzheimer disease.