Do CSF total tau, phosphorylated tau, and beta-amyloid 42 help to predict progression of mild cognitive impairment to Alzheimer's disease? A systematic review and meta-analysis of the literature

The search for biomarkers as a diagnostic aid to the identification of patients in pre-dementia stages is a fast growing research area. In view of the low specificity attained with the clinically based diagnostic criteria, including those for mild cognitive impairment (MCI), biomarker information will add precision to the incipient dementia diagnostic work-up, particularly Alzheimer's disease (AD). We present a systematic review of the literature and meta-analysis of the most relevant publications about the role of CSF biomarkers in the identification of patients with probable Alzheimer's disease at pre-dementia stages. A total of 16 studies were included in the systematic review, five of which were suitable for meta-analysis. We compared the standard mean differences (SMD) of beta-amyloid 42 (A beta 42), total tau (T-tau) and phosphorylated tau (P-tau) for 130, 169 and 123 patients with MCI who converted to AD (MCI-AD) and 142, 157 and 130 controls, respectively. We conclude that when a clinical diagnosis of MCI is made at baseline assessment, low CSF levels of A beta 42 (SMD: -1.57, CI95% [-2.30 to -0.84], P<0.001), along with high T-tau (SMD: 1.52, CI95% [1.25 to 1.79], P0.001), and high P-tau (SMD: 1.75, CI95% [0.99 to 2.51], P<0.001), help to predict the conversion to Alzheimer's disease as compared to controls subjects.