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conferenceseries
.com
Volume 7, Issue 6 (Suppl)
J Alzheimers Dis Parkinsonism, an open access journal
ISSN: 2161-0460
Dementia 2017
October 16-18, 2017
ALZHEIMER’S DISEASE & DEMENTIA
October 16-18, 2017 | Rome, Italy
9
th
International Conference on
Investigations of non-classical axis of renin angiotensin system in Alzheimer's Disease
Noura AL Mulhim, Scott Miners
and
Patrick Kehoe
University of Bristol, United Kingdom
Southmead Hospital, United Kingdom
Introduction:
The classical axis of RAS (ACE-1/Ang II/AT1R) has been highlighted as exerting damage effects on the brain
in both animal and human studies. Hyperactivity of this axis contributed to the pathogenesis of Alzheimer's disease (AD).
However, the involvement of the non-classical axis of RAS (ACE-2/Ang (1-7)/MasR) in the etiology and progression of AD
remain to be clarified. Therefore, investigating components of the non-classical axis of RAS is important for understanding the
role of this system in the pathogenesis of AD.
Methods:
Human Post-Mortem brain tissue used in this study was obtained from the South West Dementia Brain Bank,
University of Bristol, with local Research Ethics Committee approval. The AD cases (n=72) and the age-matched controls (n=
47) were selected. In this cohort, we measured Ang (1-7) levels in the mid-frontal cortex (Brodmann area 9) using in-house
direct ELISA. A commercially available ELISA kit was used to measure MAS1 levels. Data on Ang II and ACE-2 activity had
been previously obtained for all cases.
Results:
In this study, Ang (1-7) levels were unchanged in AD group compared to age-matched controls. However, Ang II/Ang
(1-7) ratio (as a proxy indicator of ACE-2 activity) was significantly increased in AD group, indicating a reduction of ACE-2
activity in AD. For the first time, we showed that the MAS1 levels were significantly reduced in AD. This reduction in MAS1
levels was correlated with reduction in ACE-2 activity.
Conclusions:
Together, our findings suggested that dysregulation of ACE-2/Ang(1-7)/MasR) axis might be implicated in the
pathogenesis of AD. Thus, maintaining the activity of the non-classical axis of RAS may be essential for targeting therapeutic
strategies of AD.
na15725@bristol.ac.ukNoura AL Mulhim et al., J Alzheimers Dis Parkinsonism 2017, 7:6(Suppl)
DOI: 10.4172/2161-0460-C1-034