Alzheimer's disease (AD) and type II diabetes mellitus (DM2) are the most common aging-related diseases and are characterized by β-amyloid and amylin accumulation, respectively.
Alzheimer's Disease (AD) and Type 2 diabetes mellitus (T2DM) are two incurable diseases both hallmarked by an abnormal deposition of the amyloidogenic peptides Aβ and Islet Amyloid Polypeptide (IAPP) in affected tissues.
Amylin, a pancreatic β-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer's disease.
A link between diabetes mellitus (DM) related islet amyloid polypeptide (IAPP) and Alzheimer's disease (AD) related amyloid-β (Aβ) has been suggested in epidemiological and clinical studies.
Additionally, amylin aggregates have been found in blood vessels and/or brain of patients with Alzheimer's disease, alone or co-deposited with β-amyloid.
Additionally, several critical gaps in the literature are discussed, such as our limited understanding of the amylin system during aging and in disease states, as well as complexities of amylin receptor signaling and of changing pathophysiology during AD progression that might underlie the seemingly conflicting or contradictory results in the amylin/AD literature.
Administration of the recombinant analog of the pancreatic amyloid amylin, Pramlintide, has shown therapeutic benefits in aging and Alzheimer's disease (AD) models, both on cognition and amyloid-β (Aβ) pathology.
Although functional studies are required to elucidate the role of rs73069071 in AD pathophysiology, our results support the recently growing evidence on the role of amylin in AD.
As naturally occurring amylin may play a role in regulating Aβ in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.
Furthermore, both AD and T2D are amyloidogenic diseases, with abnormal aggregation of amyloid-β peptide (Aβ) and islet amyloid polypeptide (IAPP) respectively contributing to cellular death and disease pathogenesis.
Furthermore, inoculation of pancreatic IAPP aggregates into the brains of AD transgenic mice resulted in more severe AD pathology and significantly greater memory impairments than untreated animals.
Here, by discussing available evidence, we posit that the amylin receptor could be considered a potential therapeutic target for AD, and present the rationale for using amylin receptor antagonists to treat this debilitating condition.
Herein, we examine the inhibitory effects of genistein on the aggregation of amyloid-β (Aβ, associated with Alzheimer's disease) and human islet amylin (hIAPP, associated with type 2 diabetes) and Aβ- and hIAPP-induced neurotoxicity using a combination of experimental and computational approaches.
However, when the concentration was high (10.24 μM), amylin lost the effects against the Aβ-induced cellular AD pathology and, together with Aβ, worsened tauopathy in neurons.
In addition, amylin deposition in the pancreas is more common in AD than in normal aging, and although there is no significant increase in cerebral Aβ deposition in T2DM, the extent of Aβ accumulation in AD correlates with T2DM duration.
In fact, AD and T2DM have comparable pathological features in the islet and brain (amyloid derived from amyloid β protein (β-amyloid) in the brain in AD and islet amyloid derived from islet amyloid polypeptide in the pancreas in T2DM).
In humans, β-amyloid and islet amyloid polypeptide (IAPP, also known as amylin) aggregations are linked to Alzheimer's disease and type-2 diabetes, respectively.
Intriguingly, amylin deposition was also detected in blood vessels and brain parenchyma of patients with late onset AD without clinically apparent diabetes.