Tau in cerebrospinal fluid: A potential diagnostic marker in Alzheimer's disease

Abstract

Cerebrospinal fluid from 70 patients with Alzheimer's disease (AD) and 96 patients with non-AD neurological diseases as well as 19 normal control subjects was surveyed by sandwich enzyme-linked immunosorbent assay to quantitate levels of the microtubule-associated protein tau in cerebrospinal fluid. The tau level was significantly increased in AD patients as compared with that in patients with non-AD neurological diseases and control subjects. Increased tau levels were found irrespective of age at onset, apolipoprotein E genotype, and clinical stage. Western blots of AD cerebrospinal fluid proteins revealed two to three tau-immunoreactive bands with an apparent molecular mass between 50 and 65 kd consistent with phosphorylated cerebrospinal fluid tau. Taken together, our results suggest that cerebrospinal fluid tau might reflect the progressive accumulation of altered tau due to the progressive death of neurons in the AD brain, and that the enzyme-linked immunosorbent assay of cerebrospinal fluid tau may prove to be a reliable and early diagnostic test for AD.

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

“…61 The 20 largest studies 14,20,24,41,50,56,[62][63][64][65][66][67][68][69][70][71][72][73][74][75] including more than 2000 AD patients and 1000 controls, evaluating the most commonly used ELISA method for T-tau in CSF, 14 are summarized in Table 2. The mean sensitivity to discriminate AD from nondemented aged individuals has been 81%, at a specificity level of 91% (Table 2).…”

A REVIEW OF BIOCHEMICAL MARKERS FOR EARLY DIAGNOSIS OF ALZHEIMER’S DISEASE

“…Increased CSF-tau is present during the whole course of the disease in Alzheimer's disease which suggests that it may be present before the onset of clinical dementia (Andreasena et al, 1998;Zetterberga et al, 2003;Arai et al, 1995;Mattsson et al, 2009). Tau is also helpful in discriminating patients of Alzheimer's disease with frontotemporal dementia 26 .…”

Geriatric Medicine, Japanese Alzheimer's Disease Neuroimaging Initiative and Biomarker Development

“…Further, validation of AD biomarkers requires confirmation by at least 2 independent studies from qualified investigators published in peer-reviewed journals. Tau and Aβ are major components of the two neuropathological hallmarks of AD (tangles and plaques respectively), and they are the most intensively studied candidate AD biomarkers where they are best studied in cerebrospinal fluid (CSF) using extensively characterized ELISAs (Arai et al 1995;Arai et al 1997;Arai et al 1998;Tomita et al 2007). A recent examination of > 100 subjects with autopsy-confirmed diagnoses reached a conclusion that elevated CSF tau levels are associated with the presence of AD pathology and CSF Aβ 42 levels are decreased in AD (Clark et al 2003).…”