Open AccessIntranasal rifampicin for Alzheimer's disease prevention
Author(s) -
Umeda Tomohiro,
Tanaka Akiko,
Sakai Ayumi,
Yamamoto Akira,
Sakane Toshiyasu,
Tomiyama Takami
Publication year - 2018
Publication title -
alzheimer's and dementia: translational research and clinical interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.49
H-Index - 30
ISSN - 2352-8737
DOI - 10.1016/j.trci.2018.06.012
Subject(s) - rifampicin , nasal administration , medicine , pharmacology , oral administration , dosing , adverse effect , pharmacokinetics , pathology , tuberculosis
Oral rifampicin has been shown to significantly reduce amyloid β (Aβ) and tau pathologies in mice. However, it shows occasional adverse effects such as liver injury in humans, making its use difficult for a long period. Methods To explore safer rifampicin treatment, APP OSK mice, a model of Alzheimer's disease, were treated with rifampicin for 1 month via oral, intranasal, and subcutaneous administration, and its therapeutic efficacy and safety were compared. Results Intranasal or subcutaneous administration of rifampicin improved memory more effectively than oral administration. The improvement of memory was accompanied with the reduction of neuropathologies, including Aβ oligomer accumulation, tau abnormal phosphorylation, and synapse loss. Serum levels of a liver enzyme significantly rose only by oral administration. Pharmacokinetic study revealed that the level of rifampicin in the brain was highest with intranasal administration. Discussion Considering its easiness and noninvasiveness, intranasal administration would be the best way for long‐term dosing of rifampicin.