CSF markers for Alzheimer's disease: Total tau, phospho-tau and Aβ42

Abstract

Today we have the first therapeutic compounds for treatment of Alzheimer's disease (AD) e.g. acetylcholine esterase inhibitors and in the near future we may expect new compounds such as γ- and β-secretase inhibitors. This has demanded increased accuracy in the diagnosis of AD and thus, among other possible approaches, diagnostic markers in the cerebrospinal fluid (CSF) have become a rapidly growing research field. Especially early in the course of the disease, when correct diagnosis is most difficult, such biomarkers would be especially valuable as one might expect the compounds to have the greatest potential of being effective. Two of the defining lesions in AD brains are senile plaques and neurofibrillary tangles with β-amyloid (Aβ) and tau proteins as the main components respectively. Aβ and tau proteins are secreted to body fluids including plasma and cerebrospinal fluid (CSF). In this paper we review CSF markers for AD, with focus on their role in the clinical diagnosis. Reduced CSF levels of the 42 amino acid form of Aβ (Aβ42) and increased CSF levels of total tau (T-tau) in AD have been found in numerous studies, with high sensitivity figures. However, the specificity against other dementias is lower. The addition of phospho tau (P-tau) seems to increase the specificity, since normal levels are found in other dementias and in cerebrovascular disease. An increasing number of studies suggests that these CSF markers perform well enough to have a role in the clinical work-up of patients with dementia if used together. We stress that the CSF markers should be combined with the clinical information and brain-imaging techniques.