Faculty Collaboration Database

Sex Differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple-Transgenic Mouse Model of Alzheimer's Disease. Neurosci Bull 2018 Oct;34(5):736-746

Date

08/14/2018

Pubmed ID

30099679

Pubmed Central ID

PMC6129237

DOI

10.1007/s12264-018-0268-9

Scopus ID

2-s2.0-85051464126 (requires institutional sign-in at Scopus site)   104 Citations

Abstract

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.

Author List

Yang JT, Wang ZJ, Cai HY, Yuan L, Hu MM, Wu MN, Qi JS

Author

Mengming Hu Postdoctoral Researcher in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alzheimer Disease
Amyloid beta-Protein Precursor
Animals
Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Disease Models, Animal
Female
Hippocampus
Humans
Inflammation
Male
Maze Learning
Mice, Inbred C57BL
Mice, Transgenic
Neurofibrillary Tangles
Plaque, Amyloid
Presenilin-1
Sex Characteristics
Spatial Memory
p38 Mitogen-Activated Protein Kinases
tau Proteins