科研之友
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摘要
AD pathology is often seen in cortical biopsies of NPH patients. It remains unclear whether these findings are coincidental or causally related. In an aged animal model of NPH, we quantify A beta and pTau accumulation and describe its temporal and spatial distribution. One-year-old male Sprague-Dawley rats had hydrocephalus induced by cisternal kaolin injection. Immunohistochemistry (IMHC) for A beta PP, A beta 40, A beta 42 and pTau (epitope pT231) and ELISA for A beta 40, A beta 42 and pT231 were performed on controls and after 2, 6 and 10 weeks of hydrocephalus. Rats had double-label fluorescence IMHC for localization of A 42 and pT231. IMHC showed no change in neuronal A beta PP expression following hydrocephalus. A beta 42 appeared earliest in CSF clearance pathways, p<0.05, and also showed significant rises in perivascular spaces and in cortical parenchyma. Mean ELISA values for A beta 40 and A beta 42 increased three- to four-fold in hydrocephalic rats at 6 and 10 weeks. A beta 40 increased between 2 and 6 weeks (p=0.0001), and remained stable at 10 (p=0.0002); whereas A beta 42 was elevated at 2 weeks (p<0.04) and remained at 6 (p=0.015). PTau at 6 and 10 weeks showed AD-like increased neuronal somatic staining and loss of dendritic staining. ELISA demonstrated increased pT231 in hydrocephalic rats at 10 weeks (p<0.0002). Double-label fluorescence for A beta 42 and pT231 revealed intraneuronal co-localization. Hydrocephalus in the elderly rat, therefore, can induce both A beta and pTau accumulation. As distinct from brain injury models, no increase in A beta PP expression was demonstrated. Rather, altered CSF dynamics appears to impair A beta clearance in this NPH model.
- 出版日期2010-3-4
