Abstract
Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM) are two of the most prevalent diseases in the elderly population worldwide. A growing body of epidemiological studies suggest that people with T2DM are at a higher risk of developing AD. Likewise, AD brains are less capable of glucose uptake from the surroundings resembling a condition of brain insulin resistance. Pathologically AD is characterized by extracellular plaques of Aβ and intracellular neurofibrillary tangles of hyperphosphorylated tau. T2DM, on the other hand is a metabolic disorder characterized by hyperglycemia and insulin resistance. In this review we have discussed how Insulin resistance in T2DM directly exacerbates Aβ and tau pathologies and elucidated the pathophysiological traits of synaptic dysfunction, inflammation, and autophagic impairments that are common to both diseases and indirectly impact Aβ and tau functions in the neurons. Elucidation of the underlying pathways that connect these two diseases will be immensely valuable for designing novel drug targets for Alzheimer's disease.
Highlights
Alzheimer’s Disease: Neuropathological Alterations and Metabolic Risk FactorsDiagnosed by the German psychiatrist and neuropathologist, Prof
These results show that firstly insulin resistance in Type 2 Diabetes Mellitus (T2DM) is capable of inducing prolonged period of oxidative stress which leads to the failure of autophagic machinery and impaired autophagic clearance
It should be noted that almost all the animal models of Aβ and tau that have been used for preclinical studies are based on FTDP-17 cases and not on sporadic Alzheimer’s disease (AD) models
Summary
Diagnosed by the German psychiatrist and neuropathologist, Prof. Alois Alzheimer in 1906, Alzheimer’s disease is the most prevalent form of dementia in the aging population (van der Flier and Scheltens, 2005). In early onset fAD, the disease pathology is caused by mutation in three known genes namely: amyloid precursor protein (APP), presenilin-1 (PS-1), and presenilin-2(PS-2). A large body of evidence supports the idea that the formation of Aβ plaques occurs 15–20 years earlier before the cognitive functions decline, whereas the spatial and temporal spread of tau pathology correlates more strongly with the severity with disease progression (Serrano-Pozo et al, 2011; Vlassenko et al, 2012). Insulin resistance arises due to decreased insulin sensitivity of muscle, liver, and fat cells to insulin Another prominent feature of T2DM is the formation of human islet amyloid polypeptide that causes pancreatic β-cell dysfunction (Marzban et al, 2003). What is the evidence that there is a patho-physiological link between Diabetes and AD?
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