Brain Alterations and Clinical Symptoms of Dementia in Diabetes: Aβ/Tau-Dependent and Independent Mechanisms

Abstract

Emerging evidence suggests that diabetes affects cognitive function and increases the incidence of dementia. However, the mechanisms by which diabetes modifies cognitive function still remains unclear. Morphologically, diabetes is associated with neuronal loss in the frontal and temporal lobes including the hippocampus, and aberrant functional connectivity of the posterior cingulate cortex and medial frontal/temporal gyrus. Clinically, diabetic patients show decreased executive function, information processing, planning, visuospatial construction, and visual memory. Therefore, in comparison with the characteristics of AD brain structure and cognition, diabetes seems to affect cognitive function through not only simple AD pathological feature-dependent mechanisms but also independent mechanisms. As an Aβ/tau-independent mechanism, diabetes compromises cerebrovascular function, increases subcortical infarction, and might alter the blood–brain barrier. Diabetes also affects glucose metabolism, insulin signaling, and mitochondrial function in the brain. Diabetes also modifies metabolism of Aβ and tau and causes Aβ/tau-dependent pathological changes. Moreover, there is evidence that suggests an interaction between Aβ/tau-dependent and independent mechanisms. Therefore, diabetes modifies cognitive function through Aβ/tau-dependent and independent mechanisms. Interaction between these two mechanisms forms a vicious cycle.

Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease

“…APs are extracellular deposits of Aβ in the grey matter of the brain and have been considered to be neurotoxic3, whereas the tau protein is a microtubule-binding protein whose main function is to maintain axonal microtubule stability. To date, the underlying mechanism linking Aβ and tau to AD still keeps uncertain145. Many testing drugs have been designed to target established mechanisms of AD, especially the removal of aggregated Aβ67.…”

Glucose levels during life and neuropathologic findings at autopsy among people never treated for diabetes

“…The mechanism by which this dysfunction may cause cognitive impairment or dementia is uncertain. The mechanism may occur through amyloid β or tau dependent or independent mechanisms (Sato and Morishita, 2014). The amyloid cascade hypothesis of Alzheimer’s disease suggests that either increased production and/or reduced clearance of amyloid β species is a key mechanistic event in the development of Alzheimer’s disease pathology.…”

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

“…Hyperglycemia and Aβ accumulation also play important roles in the memory ability of diabetic patients (Capiotti et al, 2014; Ding and Huang, 2014; Sato and Morishita, 2014). In our study, AVLT immediate recall and delayed recall tests were used to measure verbal learning and memory.…”