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J Alzheimers Dis. 2014;42 Suppl 3:S305-13. doi: 10.3233/JAD-132615.

Impact of N-Acetylcysteine on cerebral amyloid-β plaques and kidney damage in spontaneously hypertensive stroke-prone rats.

Author information

German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
Institute of Biometry and Medical Informatics, Otto-von-Guericke University, Magdeburg, Germany.
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.
Paul-Flechsig-Institute for Brain Research, Universität Leipzig, Leipzig, Germany.
Institute for Life Sciences, University of Southampton, Southampton, UK.



Cerebral small vessel disease (CSVD) in spontaneously hypertensive stroke prone rats (SHRSP) is accompanied by parenchymal amyloid-β (Aβ) deposition in the brain and by hypertensive nephropathy with tubulointerstitial damage. N-acetylcysteine (NAC) promotes blood-brain barrier (BBB) breakdown in SHRSP and may thus accelerate the failure of vascular and perivascular clearance of Aβ.


In this study, we test the hypothesis that treatment with NAC increases the cerebral Aβ load and improves renal damage in the SHRSP model.


A total of 46 SHRSP (ages 18-44 weeks) were treated daily with NAC (12 mg/kg body weight) and 74 no-treated age-matched SHRSP served as controls. The prevalence of parenchymal Aβ load, IgG positive small vessels, and small perivascular bleeds was assessed in different brain regions. Tubulointerstitial kidney damage was assessed through a) the presence of erythrocytes in peritubular capillaries and b) tubular protein cylinders.


SHRSP treated with NAC had an age-dependent increase of BBB breakdown (assessed by the presence of IgG positive small vessels) and small perivascular bleeds, mainly in the cortex. NAC significantly increased the Aβ plaque load in the cortex while the number of parenchymal amyloid deposits in the remaining brain areas including basal ganglia, hippocampus, thalamus, and corpus callosum were unchanged. There were no significant treatment effects on tubulointerstitial kidney damage.


The impact of NAC on cerebral cortical plaque load increase may result from the vascular pathology of SHRSP that accompanies BBB breakdown, leading to the failure of amyloid clearance mechanisms. It remains to be seen whether in humans chronic NAC intake may increase amyloid load in the aging human brain and dementia.


Amyloid-β; N-acetylcysteine rats; cerebral small vessel disease; hypertensive nephropathy; spontaneously hypertensive stroke prone rats (SHRSP)

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