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

Suzanne   V.   Frankfort; Linda   R.   Tulner; Jos   P.C.M.   van Campen; Marcel   M.   Verbeek; Rene   W.M.M.   Jansen; Jos   H.   Beijnen

doi:10.2174/157488408784293723

Abstract

This review addresses recent developments in amyloid β (Aβ), 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 Alzheimers Disease (AD). A combination of Aβ42 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 Aβ42 and increased tau levels) is a very strong predictor for the progression of MCI into AD. Furthermore, CSF measurements of p-tau and Aβ42 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 Aβ42 or in combination with the Aβ37/Aβ42 or Aβ38/Aβ42 ratio aids in the discrimination between AD and Lewy Body dementia remains to be elucidated. Cross-sectional research could not demonstrate significant differences for Aβ40 and Aβ42 in plasma between AD and controls. However, a recently published longitudinal study showed high baseline Aβ40 levels, especially when combined with low baseline Aβ42 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 Aβ and its transport between CSF and plasma, however, needs further clarification. In conclusion, progress has been made regarding Aβ 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 Aβ peptides), type of matrix (CSF and plasma) and data analysis (establishment of predefined cut-off values, type of ratio, type of marker combination).

Keywords: mild cognitive impairment (MCI), Amyloid precursor protein, CSF biomarkers, Lewy Body Dementia, Alzheimer disease

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