title: Degenerative alterations in noradrenergic neurons of the locus coeruleus in Alzheimer's disease.
abstract: Mice carrying mutant amyloid-β precursor protein and presenilin-1 genes (APP/PS1 double transgenic 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-β 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 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.
authors.affiliation: Department of Histology & Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China ; Department of Nursing, Medical College of Hunan Normal University, Changsha 10013, Hunan Province, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Liu
authors.affiliation: Third Department of Surgery, Agricultural Division Four Hospital, Xinjiang Production and Construction Corps, Yili 835000, Xinjiang Uygur Autonomous Region, China.
authors.forename: Saiping
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Anatomy & Neurobiology, School of Basic Medical Sciences, Central South University, Changsha 410013, Hunan Province, China.
authors.forename: Leping
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Nursing, Medical College of Hunan Normal University, Changsha 10013, Hunan Province, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Medical College of Hunan Normal University, Changsha 410013, Hunan Province, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Anatomy, Medical College of Hunan Normal University, Changsha 410013, Hunan Province, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Jian
keywords: Alzheimer's disease; grants-supported paper; locus coeruleus; neural regeneration; neuroregeneration; no-radrenergic neuron; presenilin-1; senile plaques; tyrosine hydroxylase; β-amyloid