Diabetes type 2 and Alzheimer disease – one or two diseases? Mechanisms of association

Abstract

Some epidemiological data and pathophysiological evidence suggest similarities and connection of two amyloidoses: diabetes mellitus type 2, (DM2) (non-insulin dependent diabetes mellitus, NIDDM) and Alzheimer's disease (AD). What they have in common is insulin resistance, neurodegeneration, development and progression of dementia, and the fact that in the course of both diseases fibrillar aggregates of specific proteins are accumulated in affected organs. What is more, experimental evidence also supports the hypothesis that small prefibrillar aggregates that emerge prior to the appearance of mature fibrils are responsible for a key step in development and cytotoxicity of both diseases. They also have similar pathogenic effects. Both peptides possess the common receptor AMY3. More and more evidence is accumulating that key cell regulation processes are similar for both diseases as well. The question is raised: can Alzheimer be a new form of diabetes disease?

Lychee seed extract protects against neuronal injury and improves cognitive function in rats with type II diabetes mellitus with cognitive impairment

“…IR indirectly enhances the activity of glycogen synthase kinase-3β (GSK-3β) and promotes the AD-like Tau hyperphosphorylation in the hippocampus of the mice and rats in animal models of insulin dysfunction ( 46 ). In addition, IR can regulate the activity of γ-secreting enzyme by GSK-3β ( 47 ), promote the synthesis of Aβ40 and Aβ42, inhibit the activity of insulin degrading enzyme and reduce the degradation of Aβ ( 48 ). Furthermore, insulin plays a pivotal role in regulation of energy metabolism, growth, survival and differentiation of neuronal cells via insulin signaling in the brain ( 49 , 50 ).…”

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

“…As noted in the Introduction, the two diseases present abnormal blood glucose levels, insulin resistance, inflammation, oxidative stress, and neurodegeneration [42, 43]. Nowadays, three ChE inhibitors can be used to delay the symptomatic decline observed in patients with AD.…”

Potential Role of Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Cognitive Decline and Dementia in Diabetes Mellitus

“…Loss of white matter is most evident in the frontal and temporal regions, whereas loss of gray matter is most evident in the medial temporal, anterior cingulate, and medial frontal lobes [29]. Regarding the risk of MCI in T2DM patients, epidemiological studies have revealed hazard ratios (HRs) of 1.5 and 1.2 for amnesic MCI and non-amnesic MCI [13,25,[30][31][32], respectively. In addition, a meta-analysis has indicated a relative risk of conversion of MCI to dementia of 1.7 (1.1-2.4) for individuals with T2DM compared to individuals without diabetes [33].…”