gms | German Medical Science

58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

26. bis 29.04.2007, Leipzig

Evidence of Alzheimer-related pathology in aged rats with kaolin-induced hydrocephalus

Nachweis von Alzheimerpathologie bei alternden Ratten mit Kaolin-induziertem Hydrozephalus

Meeting Abstract

  • corresponding author P. Klinge - International Neuroscience Institute, Hannover, Deutschland
  • A. Samii - International Neuroscience Institute, Hannover, Deutschland
  • A. Akhmetshina - International Neuroscience Institute, Hannover, Deutschland
  • C. Johanson - Brown Medical School, Providence, Rhode Island, US
  • T. Brinker - International Neuroscience Institute, Hannover, Deutschland
  • G. Silverberg - Stanford University Medical School, California, US

Deutsche Gesellschaft für Neurochirurgie. 58. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC). Leipzig, 26.-29.04.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. DocDO.03.09

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2007/07dgnc027.shtml

Veröffentlicht: 11. April 2007

© 2007 Klinge et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: 30-50% of shunted normal pressure hydrocephalus patients show amyloid (A-beta) plaques and neurofibrillary tangles, consistent with Alzheimer’s disease (AD), on cortical biopsy. Decreased A-beta clearance via cerebrospinal fluid (CSF) and vascular endothelium at the blood-brain barrier (BBB) may be causative. We investigated A-beta accumulation, A-beta transport and TAU pathology in aged hydrocephalic rat brains.

Methods: Kaolin-hydrocephalus was induced in 12 months old Sprague-Dawley rats (n=15). Untreated age-matched rats served as controls (n=5). A-beta and hyper-phosphorylated tau (hpTau) accumulation was investigated by specific A-beta40, A-beta42 and hpTau (pT231 and AT100) antibody immunohistochemistry performed 2, 6 and 10 weeks after hydrocephalus induction. The expression of two specific BBB-endothelial A-beta receptors was assessed by immunohistochemistry, RT-PCR and Western blotting: LRP-1, which transports A-beta out of, and RAGE, which transports A-beta into the central nervous system.

Results: In hydrocephalus, both A-beta 42 and A-beta 40 staining show increased cortical and subcortical endothelial and perivascular A-beta accumulations. At 6 and 10 weeks, parenchymal, neuronal and cortical vascular A-beta accumulations were pronounced. Also staining of hpTau showed a progressive increase in both intra- and extracellular locations. Extracellular staining of paired-helical-filament (PHF) TAU AT100 occurred in the hippocampus at 6 weeks. However, in the larger cortical pyramidal neurons, migration of hyperphosphorylated pre-tangle TAU (pT231) from neuronal dendrites to the soma occurred, as seen in AD. LRP expression was markedly decreased in cortical and hippocampal microvessels, most prominent after 6 weeks. RAGE expression showed changes opposite to LRP-1.

Conclusions: In our model, vascular and interstitial A-beta and neuronal hpTau antibody staining increased the longer the hydrocephalus persisted. In addition to the disturbed clearance via CSF in hydrocephalus, the altered endothelial receptor expressions indicated impairment of A-beta clearance mechanisms through the vascular route. A-beta does accumulate in hydrocephalus and may lead to hpTau formations, which have been shown to be involved in the fibrillogenic process in AD. This raises evidence towards a common pathophysiology underlying both diseases, AD and Normal pressure hydrocephalus.