Status of Acetylcholinesterase and Butyrylcholinesterase in Alzheimer's Disease and Type 2 Diabetes Mellitus

Abstract

Both Alzheimer’s disease (AD) and Type 2 diabetes mellitus (T2DM) share the presence of systemic and neuro-inflammation, enhanced production and accumulation of β-amyloid peptide and abnormal levels of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Altered levels of AChE and BuChE both in AD as well as in T2DM imply that those two enzymes may be playing a pivotal role in the pathogenesis of the two disorders. AD and T2DM are both characterized by elevated levels of AChE and BuChE in the plasma. On the other hand, in AD the brain levels of AChE go down while those of BuChE go up, resulting in deregulation in balance between AChE and BuChE. This imbalance and change in the AChE/BuChE ratio causes cholinergic deficit in the brain, i.e. deficiency in the brain neurotransmitter acetylcholine. With better understanding of the inter-relationship of AChE and BuChE levels in normality as well as abnormality, AD and T2DM can be effectively treated. Thus, general cholinesterase inhibitors that inhibit both AChE and BuChE as well as highly selective BuChE inhibitors may have potential therapeutic benefits in the treatment of AD and other related dementias.

The activity of blood serum cholinesterases and neprilysin as potential biomarkers of mild-cognitive impairment and Alzheimer’s disease

“…В то же время активность АХЭ и бутирилхолинэстеразы (ЕС 3.1.1.8, БХЭ) в коре головного мозга и цереброспинальной жидкости в ходе старения и при БА также снижается [30,31]. При этом в ткани мозга изменяется соотношение активности АХЭ и БХЭ [32,33]. Также показано наличие прямой корреляции между уров-нем активности АХЭ в плазме крови и числом амилоид-ных депозитов в мозге при БА [34].…”

The diabetic brain and cognition

“…As levels of that enzyme are altered in T2DM too, those authors suggest a synergistic negative interaction of T2DM and AD on cholinergic neurotransmission (Mushtaq et al 2014). Among common pathogenic factors between DM and AD, BChE has been studied in vitro and in plasma (Sridhar et al 2006;Rao et al 2007;Shaikh et al 2014).…”

Development of Chronic Diabetic Complications and Role of Porphyrin Derivatives in Reducing Inflammation in Type 2 Diabetes Mellitus

“…Some recent studies have shown that plasma and tissue concentrations of Acetylcholinesterase are increased in type 2 Diabetes Mellitus. Since Acetylcholine has anti-inflammatory action, therefore, high level of Acetylcholinesterase concentration can decrease the level of acetylcholine available to trigger systemic inflammation [10]. Hence, prevention of over-expression of AchE is an ideal strategy to inhibit the development of chronic complications of Diabetes.…”