The team used TgCRND8 AD
mice and nontransgenic littermates (as controls). The mice were provided by The
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto,
Canada. Only female mice were used as male littermates were aggressive. The
team obtained 70 female mice through
- 7 TgCRND8 and 33 wild-type
Two-month old TgCRND8 AD
mice and nontransgenic littermates were randomized into groups which received
food supplemented with 5 mg/g of dabigatran etexilate (BIBR 1048) or placebo.
Both drug and placebo were provided by Boehringer Ingelheim, Germany. The mice
were treated till they were 30 weeks old.
team found that AD mice treated with dabigatran were able to successfully negotiate
the test of Barnes maze to assess spatial memory at 25 weeks whereas placebo
treated mice were not up to the task.
The mice were then
sacrificed at 30 to 60 weeks and blood and brain tissue were collected for
histology and immunohistochemistry.
The mice treated with dabigatran showed positive improvement with prevention of memory decline
improved blood flow in the cerebral area and reduction of toxic fibrin deposits
in the brain. The dabigatran treated mice also showed reduction in the deposit
of amyloid plaques, oligomers, phagocytic microglia and infiltrated T cells.
This study proved that long term use of dabigatran can prevent cognitive
decline, improve cerebral blood flow, reduce amyloid
and reduce neuroinflammation. Dabigatran actually inhibited
thrombin and excessive deposition of fibrin in the brain thereby preserving
blood flow, facilitating oxygen and rich nutrient delivery to the brain. The
results open up a new field to study how this can be translated to therapeutic
benefits for Alzheimer's patients.
- Long-Term Dabigatran Treatment Delays Alzheimer's Disease Pathogenesis in the TgCRND8 Mouse Model - (http://www.onlinejacc.org/content/74/15/1910)