The Cerebrospinal Fluid Levels of Tau, Growth-Associated Protein-43 and Soluble Amyloid Precursor Protein Correlate in Alzheimer’s Disease, Reflecting a Common Pathophysiological Process

Abstract

Cerebrospinal fluid (CSF) levels of tau (total tau), growth-associated protein-43 (GAP-43), soluble amyloid precursor protein (sAPP; i.e. total sAPP), and β-amyloid₄₂ (Aβ₄₂) were studied in patients with frontotemporal dementia (FTD; n = 14), Alzheimer’s disease (AD; n = 47) and vascular dementia (VAD; n = 16), and in age-matched controls (n = 12). CSF-tau was increased in AD compared to controls and FTD (p < 0.001 for both). CSF-GAP-43 was increased in AD compared to controls (p < 0.05), and both CSF-GAP-43 and CSF-sAPP were increased in AD compared to FTD (p < 0.01). Positive and highly significant correlations were found between CSF-tau and CSF-GAP-43 in all groups and between CSF-tau, CSF-GAP-43 and CSF-sAPP in AD. The correlations found may reflect a common pathophysiologic process such as axonal degeneration.

Tau Monoclonal Antibody Generation Based on Humanized Yeast Models

“…For optimal comparison, we also included a calibrator peptide, allowing us to convert OD values into concentration values (pg/ml). Consistent with data reported previously (35)(36)(37), the levels of total Tau were significantly increased in samples of VAD and AD patients as compared with those of the healthy controls (Fig. 9).…”

“…This is in agreement with previously published studies (35)(36)(37). Recently, improved characterization of CSF Tau using reverse-phase high performance liquid chromatography led to the evaluation of five total Tau assays side by side, and the two assays containing N-terminal sequences exhibited the most significant differences between AD and control CSF (66).…”

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).…”

“…Most studies have found normal to mildly increased CSF T-tau levels in other dementias, such as frontotemporal dementia (FTD) 14,15,21,50,52,69,70,73,[82][83][84][85][86] and Lewy body dementia (LBD). [85][86][87][88][89][90] Other than in aged nondemented individuals, normal CSF T-tau is found in depression, alcoholic dementia, and in chronic neurological disorders such as Parkinson's disease (PD) and progressive supranuclear palsy.…”

“…139 In AD, increased CSF levels of GAP43 are found, although CSF GAP43 is normal in FTD and in PD. 50,69,140 There is a clear correlation between the CSF levels of T-tau and GAP 50,69 and some data suggest that the ratio of CSF GAP43/T-tau may be of diagnostic importance. 50 However, further studies are needed on the potential of GAP43 as a diagnostic marker for AD.…”