Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer＇s disease

Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correla...

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Bibliographic Details
Published in:Neural regeneration research 2013-08, Vol.8 (24), p.2249-2255
Main Authors: Liu, Lihua, Luo, Saiping, Zeng, Leping, Wang, Weihong, Yuan, Liming, Jian, Xiaohong
Format: Article
Language:English
Subjects:
Age
Alzheimer's disease
Brain
Cytokines
Dementia
Memory
Morphology
Pathology
Proteins
Quantitative analysis
Rodents
Studies
Transgenic animals
淀粉样前体蛋白
肾上腺素能
蓝斑
转基因小鼠
酪氨酸羟化酶
阳性神经元
阿尔茨海默氏病
阿尔茨海默氏症
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Summary:Mice carrying mutant amyloid precursor protein and presenilin-1 genes （APP/PS1 double trans- genic mice） have frequently been used in studies of Alzheimer＇s disease; however, such studies have focused mainly on hippocampal and cortical changes. The severity of Alzheimer＇s disease is known to correlate with the amount of amyloid-13 protein deposition and the number of dead neurons in the locus coeruleus. In the present study, we assigned APP/PS1 double transgenic mice to two groups according to age： young mice （5-6 months old） and aged mice （16-17 months old）. Age-matched wild-type mice were used as controls. Immunohistochemistry for tyrosine hydroxylase （a marker of catecholaminergic neurons in the locus coeruleus） revealed that APP/PS1 mice had 23% fewer cells in the locus coeruleus compared with aged wild-type mice. APP/PS1 mice also had increased numbers of cell bodies of neurons positive for tyrosine hydroxylase, but fewer tyrosine hydroxylase-positive fibers, which were also short, thick and broken. Quantitative analysis using unbiased stereology showed a significant age-related increase in the mean volume of tyrosine hy- droxylase-positive neurons in aged APP/PS1 mice compared with young APP/PS1 mice. Moreover, the mean volume of tyrosine hydroxylase-positive neurons was positively correlated with the total volume of the locus coeruleus. These findings indicate that noradrenergic neurons and fibers in the locus coeruleus are predisposed to degenerative alterations in APP/PS1 double transgenic mice.
ISSN:1673-5374
1876-7958
DOI:10.3969/j.issn.1673-5374.2013.24.004