TY - JOUR
T1 - Behavioral and neurobiological markers of Alzheimer's disease in Ts65Dn mice
T2 - Effects of estrogen
AU - Hunter, Christopher L.
AU - Bimonte-Nelson, Heather A.
AU - Nelson, Mathew
AU - Eckman, Christopher B.
AU - Granholm, Ann Charlotte
N1 - Funding Information:
Thanks are due to Mr. John Barber and Mr. Alfred Moore for excellent technical assistance. We thank Takeda Chemical Industries for their generous gifts of BNT77 and BC05. This work was supported by USPHS grants AG04418 and AG12122.
PY - 2004/8
Y1 - 2004/8
N2 - Individuals with Down's syndrome (DS) develop neuropathological features similar to Alzheimer's disease (AD) early in life, including dementia, accumulation of β-amyloid, and irregular phosphorylation of tau proteins. Ts65Dn mice, an animal model of DS, provide a unique method to investigate the mechanisms related to AD-like symptoms in DS and possible therapeutic interventions. Ts65Dn mice undergo a decline in cholinergic phenotype and cognitive deterioration beginning at 6-8 months of age. In middle-aged female Ts65Dn mice, estrogen supplementation alleviated these cholinergic and cognitive impairments. The current study investigated AD-like markers and the effects of estrogen in male Ts65Dn mice. Estrogen treatment prior to behavioral testing did not improve cognitive deficits in 6-month-old male Ts65Dn mice, but decreased total and phosphorylated (pS199) tau in the entorhinal cortex compared to normosomic animals. Hippocampal β-amyloid(1-42) levels were increased in Ts65Dn animals, regardless of estrogen treatment. These findings further support Ts65Dn mice as a model for specific AD-like symptoms, and demonstrate that estrogen treatment of this type does not improve the cognitive ability of male Ts65Dn mice.
AB - Individuals with Down's syndrome (DS) develop neuropathological features similar to Alzheimer's disease (AD) early in life, including dementia, accumulation of β-amyloid, and irregular phosphorylation of tau proteins. Ts65Dn mice, an animal model of DS, provide a unique method to investigate the mechanisms related to AD-like symptoms in DS and possible therapeutic interventions. Ts65Dn mice undergo a decline in cholinergic phenotype and cognitive deterioration beginning at 6-8 months of age. In middle-aged female Ts65Dn mice, estrogen supplementation alleviated these cholinergic and cognitive impairments. The current study investigated AD-like markers and the effects of estrogen in male Ts65Dn mice. Estrogen treatment prior to behavioral testing did not improve cognitive deficits in 6-month-old male Ts65Dn mice, but decreased total and phosphorylated (pS199) tau in the entorhinal cortex compared to normosomic animals. Hippocampal β-amyloid(1-42) levels were increased in Ts65Dn animals, regardless of estrogen treatment. These findings further support Ts65Dn mice as a model for specific AD-like symptoms, and demonstrate that estrogen treatment of this type does not improve the cognitive ability of male Ts65Dn mice.
KW - Alzheimer's disease
KW - Down's syndrome
KW - Estradiol
KW - Tau
KW - Tau (pS199)
KW - Working memory load
KW - β-Amyloid
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U2 - 10.1016/j.neurobiolaging.2003.10.010
DO - 10.1016/j.neurobiolaging.2003.10.010
M3 - Article
C2 - 15212841
AN - SCOPUS:3042521332
SN - 0197-4580
VL - 25
SP - 873
EP - 884
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 7
ER -