Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 25, 2015; 6(12): 1223-1242
Published online Sep 25, 2015. doi: 10.4239/wjd.v6.i12.1223
Molecular and biochemical trajectories from diabetes to Alzheimer’s disease: A critical appraisal
Rajat Sandhir, Smriti Gupta
Rajat Sandhir, Smriti Gupta, Department of Biochemistry, Panjab University, Chandigarh 160014, India
Author contributions: Sandhir R and Gupta S contributed to this paper.
Conflict-of-interest statement: Authors have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Rajat Sandhir, Professor, Department of Biochemistry, Panjab University, Sector 14, Chandigarh 160014, India. sandhir@pu.ac.in
Telephone: +91-172-2534131-38
Received: May 6, 2015
Peer-review started: May 8, 2015
First decision: July 10, 2015
Revised: August 26, 2015
Accepted: September 7, 2015
Article in press: September 8, 2015
Published online: September 25, 2015
Processing time: 160 Days and 1 Hours
Abstract

Diabetes mellitus (DM), a metabolic disorder is a major orchestra influencing brain and behavioral responses via direct or indirect mechanisms. Many lines of evidence suggest that diabetic patients apparently face severe brain complications, but the story is far from being fully understood. Type 2 diabetes, an ever increasing epidemic and its chronic brain complications are implicated in the development of Alzheimer’s disease (AD). Evidences from clinical and experimental studies suggest that insulin draws a clear trajectory from the peripheral system to the central nervous system. This review is a spot light on striking pathological, biochemical, molecular and behavioral commonalities of AD and DM. Incidence of cognitive decline in diabetic patients and diabetic symptoms in AD patients has brought the concept of brain diabetes to attention. Brain diabetes reflects insulin resistant brain state with oxidative stress, cognitive impairment, activation of various inflammatory cascade and mitochondrial vulnerability as a shared footprint of AD and DM. It has become extremely important for the investigators to understand the patho-physiology of brain complications in diabetes and put intensive pursuits for therapeutic interventions. Although, decades of research have yielded a range of molecules with potential beneficial effects, but they are yet to meet the expectations.

Keywords: Diabetes mellitus; Alzheimer’s disease; Insulin; Type 2 diabetes; Type 3 diabetes

Core tip: This review provides a synopsis in which a metabolic disturbance becomes indispensible for life and emerges as a molecular signal defect leading to a syndrome with multiple complications. Insulin is a spotlight player which draws a trajectory from diabetes to Alzheimer’s disease with multiple divergence and convergence. We have discussed their interplay to speculate their shared molecular footprints. These biochemical and molecular commonalities provide a clue to the investigators to look inside a therapy with a common experimental and clinical platform and also provide an insight for new interventions as future perspective to find a potential stone to kill two birds together.