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.
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.
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.
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.
One hypothesis is that the link between DM and AD is related to the function of insulin-degrading enzyme (IDE), an enzyme that degrades not only insulin and pancreatic amylin but also beta-amyloid (Abeta).
Such mechanisms include islet amyloid polypeptide (or amylin) deposition, co-localized with beta-amyloid and found in more abundance in the AD temporal cortex, blood-brain barrier breakdown and dysfunction, potentially related to pericyte degeneration, and disturbance of brain lymphatics, both in the glial lymphatic system and the newly discovered discrete central nervous system lymph vessels.
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.
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.
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.
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.
The interaction of the intrinsically disordered polypeptide islet amyloid polypeptide (IAPP), which is associated with type 2 diabetes (T2D), with the Alzheimer's disease amyloid-β (Aβ) peptide modulates their self-assembly into amyloid fibrils and may link the pathogeneses of these two cell-degenerative diseases.
Stratification by BMI classification, median fat mass, median HOMA-IR, median insulin, and median amylin were all metabolic or anthropometric factors which significantly interacted with sRAGE profiles within AD subjects.
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.
Studies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer's disease (AD) biomarkers in the blood of AD mouse models and AD patients.
Our findings uncover a previously unknown function for the IAPP/Aβ cross-amyloid interaction and suggest that conversion of Aβ or IAPP into lysosome-targeted and easily degradable hetero-oligomers by heteroassociation with IAPP mimics could become a promising approach to specifically prevent amyloid-mediated inflammation in AD, T2D, or both diseases.
Recent studies show that peripheral treatments with amylin or its clinical analog, pramlintide, reduced several components of AD pathology, including amyloid plaques, tauopathy, neuroinflammation and other components in the brain, corresponding with improved learning and memory in AD mouse models.
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.