Amyloid Beta Protein and Tau in Cerebrospinal Fluid and Plasma as Biomarkers for Dementia: A Review of Recent Literature

This review addresses recent developments in amyloid beta (A beta), total tau (t-tau) and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the progression of patients with mild cognitive impairment (MCI) into dementia and the differential diagnosis of Alzheimer's Disease (AD). A combination of A beta 42 and t-tau in CSF can discriminate between patients with stable MCI and patients with progressive MCI into AD or other types of dementia with a sufficient sensitivity and specificity. Regression analyses demonstrated that pathological CSF (with decreased A beta 42 and increased tau levels) is a very strong predictor for the progression of MCI into AD. Furthermore, CSF measurements of p-tau and A beta 42 can assist in diagnosing vascular dementia or frontotemporal dementia in the differential diagnosis of AD indicated by a reasonable sensitivity and specificity. Whether tau in combination with A beta 42 or in combination with the A beta 37/A beta 42 or A beta 38/A beta 42 ratio aids in the discrimination between AD and Lewy Body dementia remains to be elucidated. Cross-sectional research could not demonstrate significant differences for A beta 40 and A beta 42 in plasma between AD and controls. However, a recently published longitudinal study showed high baseline A beta 40 levels, especially when combined with low baseline A beta 42 levels, is a strong risk factor for the development of dementia. This emphasises the importance of performing longitudinal studies in addition to cross-sectional ones. The origin of plasma A beta and its transport between CSF and plasma, however, needs further clarification. In conclusion, progress has been made regarding A beta and tau as biomarkers for dementia both for differentiation between stable MCI and progressive MCI patients and for the differential diagnosis of AD. Future research should aim to validate these recently published results, preferably in pathologically confirmed AD patients. In addition, it is important to standardise research in terms of study design (longitudinal, minimal follow-up period of 5 years), type of researched parameters (total or p-tau, type of A beta peptides), type of matrix (CSF and plasma) and data analysis (establishment of predefined cut-off values, type of ratio, type of marker combination).