Molecular linkages between diabetes and Alzheimer's disease: current scenario and future prospects.
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.
Tanveer A
TA
Dar
Ishfaq A
IA
Sheikh
Showkat A
SA
Ganie
Riyasat
R
Ali
Laishram R
LR
Singh
Siew Hua
SH
Gan
Mohammad A
MA
Kamal
Department of Clinical Biochemistry, University of Kashmir, Hazratbal-190006, Srinagar. tanveerprl@gmail.com.
Mohammad A
MA
Zargar
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological