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Evidence of TAU pathology in kaolin-induced hydrocephalus model of the aged rat


Accumulation of A-beta peptides and hyperphosphorylated Tau (hpTAU) has been observed in immunohistochemical (IHC) studies of kaolin-induced hydrocephalus in the aged rat. Defective clearance via CSF and altered transport via blood brain barrier receptor expressions was suggested to be causal [1]. The present study reports further evidence to the significance of A-beta and TAU pathology as disease mechanisms in hydrocephalus using quantitative A-beta and hpTAU ELISA in addition to IHC studies of the lipid oxygenase 12/15 enzyme (LOX12/15), a marker of the cytokine-induced inflammation in Alzheimer disease (AD).

Materials and methods

In nine 12 month-old Sprague-Dawley (SD) rats with kaolin-induced hydrocephalus, A-beta 40 and 42 and hpTau pT231 ELISA was performed at 2, 6 and 10 weeks post induction (3 age-matched controls) in cortical plus subcortical tissue homogenates. Specific LOX12/15 (1:1000, BIOZOL/CAYMAN) IHC was performed in another 20 animals (5 controls) at the same time points including double-label fluorescent IHC using CY2 and CY3 conjugated secondary antibodies for co-localizations of A-beta 42, LOX12/15, hpTau pT231 and hpTau AT100.


A-beta 42 and 40 ELISA shows a significant increase over the course of hydrocephalus at 6 and 10 weeks post-induction when compared to the controls, e.g., A-beta 40 (pg/mg): 9.7 ± 1.3 and 9.5 ± 0.5 (6,10 wk) vs. 3.2 ± 1.2 (controls); p < 0.01 (ANOVA). HpTAU pT231 ELISA increased at 10 wk post-induction to 56.4 ± 17.3 from 28.5 ± 17.2 pg/mg in controls (p < 0.01). In hydrocephalus, LOX12/15 positive staining appeared in both cortical and hippocampal neurons, in glial processes (near vessels) and in hippocampal microglia-type cells. Image analysis (CellF©, OLYMPUS) revealed an increased number of LOX12/15 positive particles in the cortex of the hydrocephalic animals compared to controls (p < 0.05, unpaired t-test). Extracellular AT100 was clearly co-localized with the A-beta 42 around hippocampal vessels, while hpTAU pT312 IHC showed intraneuronal co-localisation at areas with "condensed excess" Tau. Intraneuronal A-beta 42 as well as pT231 was further co-localized with LOX12/15 in some cortical regions.


The findings of a 3–4 fold increase in A-beta is consistent with the amyloid burden in patients with early AD (Braak I). The increase in the amount of hpTAU at 10 wk as well as the co-localization pattern of the hpTAU markers with the A-beta supports that A-beta accumulation induces TAU pathology. LOX12/15 findings add further evidence that the aged hydrocephalic rats might be a valid model for investigating the NPH/AD pathophysiological continuum.


  1. Klinge PM, Samii A, Niescken S, Brinker T, Silverberg GD: Brain amyloid accumulates in aged rats with kaolin-induced hydrocephalus. Neuroreport. 2006, 17: 657-660. 10.1097/00001756-200604240-00020.

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Correspondence to Petra M Klinge.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Klinge, P.M., Heile, A., Slone, S. et al. Evidence of TAU pathology in kaolin-induced hydrocephalus model of the aged rat. Fluids Barriers CNS 6 (Suppl 1), S37 (2009).

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