Molecular Linkages Between Diabetes and Alzheimer's Disease: Current Scenario and Future Prospects
Tanveer A. Dar, Ishfaq A. Sheikh, Showkat A. Ganie, Riyasat Ali, Laishram R. Singh, Siew Hua Gan, Mohammad A. Kamal and Mohammad A. Zargar
Pages 290-298 (9)
After the revolutionary Rotterdam study that suggested there was an increased risk of developing Alzheimer’s
disease (AD) in patients with type-2 diabetes mellitus (T2DM), a number of studies have provided direct evidence for the
linkage between AD and T2DM. In recent years, AD is considered as a neuroendocrine disorder, also referred as type-3
diabetes. There is a growing list of evidence to suggest that, in addition to impaired insulin signaling, there are a number
of additional factors that may act as mechanistic links between AD and T2DM. These factors mainly include
hypercholesterolemia, dyslipidemia, hypercystinemia, inflammation, impaired insulin signaling and impaired central
nervous response to the adipose tissue-derived hormone leptin. Increased cholesterol plays a crucial role in the abnormal
metabolism of the amyloid precursor protein, leading to the accumulation of β-amyloid. In addition to impaired insulin
signaling, diabetes has been found to accelerate the appearance of cerebrovascular inflammation and β-amyloid peptide
(Aβ) deposition. Increased oxidative stress and production of advanced glycation end products are other probable marker
linkages. However, the details of many of these molecular links still require extensive investigation. It is possible that a
number of common molecular linkages exist between T2DM and AD. Understanding and analyzing the various molecular
linkages between AD and T2DM may shed light on new tools that can be used for the early diagnosis and treatment of
AD and also accelerate the identification of T2DM patients who are at high risk of AD.
Alzheimer’s diseases, diabetes, inflammation, insulin resistance, amyloid peptide, acetylcholine, oxidative stress,
mitochondrial dysfunction, conformational diseases, telomere shortening.
Department of Clinical Biochemistry, University of Kashmir, Hazratbal-190006, Srinagar.