Long-Term Effects of Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting over 10% of the elderly population. Epidemiological evidence indicates that traumatic brain injury (TBI) is an important risk factor for developing AD later in life. However, which injury-induced processes that contr...

Full description

Bibliographic Details
Published in:Journal of Alzheimer's Disease
Main Authors: Zysk, Marlena, Clausen, Fredrik, Aguilar, Ximena, Sehlin, Dag, Syvänen, Stina, Erlandsson, Anna
Format: Article in Journal/Newspaper
Language:English
Published: Uppsala universitet, Geriatrik 2019
Subjects:
Alzheimer's disease
amyloid-beta
inflammation
Morris water maze
neurodegeneration astrocytes
PET
traumatic brain injury
Neurology
Neurologi
Arctic
Online Access:http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-400408
https://doi.org/10.3233/JAD-190572
Description
Summary:Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting over 10% of the elderly population. Epidemiological evidence indicates that traumatic brain injury (TBI) is an important risk factor for developing AD later in life. However, which injury-induced processes that contribute to the disease onset remains unclear. The aim with the present study was to identify cellular processes that could link TBI to AD development, by investigating the chronic impact of two different injury models, controlled cortical impact (CCI) and midline fluid percussion injury (mFPI). The trauma was induced in 3-month-old tg-ArcSwe mice, carrying the Arctic mutation along with the Swedish mutation, and the influence of TBI on AD progression was analyzed at 12- and 24-weeks post-injury. The long-term effect of the TBI on memory deficiency, amyloid-beta (A beta) pathology, neurodegeneration and inflammation was investigated by Morris water maze, PET imaging, immunohistochemistry, and biochemical analyses. Morris water maze analysis demonstrated that mice subjected to CCI or mFPI performed significantly worse than uninjured tg-ArcSwe mice, especially at the later time point. Moreover, the injured mice showed a late upregulation of reactive gliosis, which concurred with a more pronounced A beta pathology, compared to uninjured AD mice. Our results suggest that the delayed glial activation following TBI may be an important link between the two diseases. However, further studies in both experimental models and human TBI patients will be required to fully elucidate the reasons why TBI increases the risk of neurodegeneration.

Similar Items