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Key observations supporting the brain insulin resistance hypothesis include: Insulin receptors in the brain (particularly the hippocampus) are downregulated in Alzheimer's patients, with reduced insulin signaling through the PI3K/Akt pathway Intranasal insulin improves cognitive function in patients with Alzheimer's and mild cognitive impairment in multiple clinical trials Type 2 diabetes increases Alzheimer's risk by 50-100%, even after adjusting for vascular risk factors Insulin degrading enzyme (IDE) is a major clearance pathway for both insulin and amyloid-ฮฒ
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