The Interplay between Diabetes and Alzheimer’s Disease—In the Hunt for Biomarkers

Abstract

The brain is an organ in which energy metabolism occurs most intensively and glucose is an essential and dominant energy substrate. There have been many studies in recent years suggesting a close relationship between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) as they have many pathophysiological features in common. The condition of hyperglycemia exposes brain cells to the detrimental effects of glucose, increasing protein glycation and is the cause of different non-psychiatric complications. Numerous observational studies show that not only hyperglycemia but also blood glucose levels near lower fasting limits (72 to 99 mg/dL) increase the incidence of AD, regardless of whether T2DM will develop in the future. As the comorbidity of these diseases and earlier development of AD in T2DM sufferers exist, new AD biomarkers are being sought for etiopathogenetic changes associated with early neurodegenerative processes as a result of carbohydrate disorders. The S100B protein seem to be interesting in this respect as it may be a potential candidate, especially important in early diagnostics of these diseases, given that it plays a role in both carbohydrate metabolism disorders and neurodegenerative processes. It is therefore necessary to clarify the relationship between the concentration of the S100B protein and glucose and insulin levels. This paper draws attention to a valuable research objective that may in the future contribute to a better diagnosis of early neurodegenerative changes, in particular in subjects with T2DM and may be a good basis for planning experiments related to this issue as well as a more detailed explanation of the relationship between the neuropathological disturbances and changes of glucose and insulin concentrations in the brain.

Diagnostic Accuracy of Blood-Based Biomarker Panels: A Systematic Review

“…The discovery of brain-specific insulin signaling deficit and insulin resistance in AD pathogenesis has led to the recent denomination of AD as “Type-3-Diabetes” ( Kandimalla et al, 2017 ; Leszek et al, 2017 ; Tt et al, 2020 ). Several recent studies have investigated and reviewed peripheral biomarkers common to both diseases with promising results ( Movassat et al, 2019 ; Kubis-Kubiak et al, 2020 ; Pekkala et al, 2020 ; Pereira et al, 2021 ). However, although extensive research has been conducted to understand underlying biological mechanisms that link AD and diabetes, the vast majority of evidence is based on animal models and observational clinical studies.…”

Pathology, Risk Factors, and Oxidative Damage Related to Type 2 Diabetes‐Mediated Alzheimer’s Disease and the Rescuing Effects of the Potent Antioxidant Anthocyanin

“…Therefore, the chances of the release of ROS will be greater in the brain than in other organs. Elevated oxidative stress by different mechanisms causes neuronal cell loss and neurodegeneration [86][87][88]. Oxidative stress plays a crucial role in the development of T2D-mediated Alzheimer's pathology.…”

The Potential Utility of Prebiotics to Modulate Alzheimer’s Disease: A Review of the Evidence

“…T2DM and AD have been known to share several pathophysiological features including hyperglycemia leading to increased Aβ production, and impaired glucose transport and subsequent glucose metabolism [52]. A new potential AD biomarker, S100B, has been investigated to learn the common pathophysiology of these diseases [53]. A cross-sectional study conducted with 100 South Indian AD patients showed that elevated levels of S100B protein in serum were significantly associated with clinical dementia rating scores compared to healthy controls [54].…”