INSULIN RESISTANCE CAUSES ALZHEIMER'S DISEASE?

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects cognitive function. It is the most common cause of dementia, accounting for 60-70% of cases worldwide. The disease is characterized by memory loss, confusion, and a gradual decline in the ability to perform everyday activities. AD imposes a significant socioeconomic burden, with costs expected to rise dramatically in the coming years.

Dementia encompasses a range of neuropsychiatric symptoms leading to a decline in cognitive function due to brain tissue degeneration. Over 55 million people worldwide suffer from dementia, with 10 million new cases emerging annually. The financial and emotional impact on patients and caregivers is substantial, with global costs estimated at USD 1.3 trillion in 2019, projected to reach 2.8 trillion by 2030.

AD is marked by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau protein in the brain. These pathological features disrupt cell function and trigger neurodegenerative processes. Aβ is produced from amyloid precursor protein (APP) through the action of β- and γ-secretases, while tau proteins stabilize microtubules but become pathological when hyperphosphorylated.

The APP gene, located on chromosome 21, produces a protein involved in neurotrophic support and cell adhesion. Tau proteins, essential for microtubule stability, become toxic when hyperphosphorylated, leading to cytoskeletal disruption and neuronal death.

Insulin resistance has been increasingly recognized as a critical factor in AD pathogenesis. The brain's glucose metabolism declines years before dementia symptoms appear, suggesting a metabolic dysfunction at play. AD has been referred to as "type 3 diabetes" due to the significant overlap with insulin resistance-related metabolic issues. 

The brain relies on glucose for energy, and any disruption in glucose metabolism can affect cognitive function. In insulin resistance, the brain's ability to use glucose is impaired, which can lead to neurodegeneration and cognitive decline.

Insulin is crucial for brain function, affecting synaptic plasticity, neurogenesis, and cognitive functions. Insulin receptors in the brain, particularly in areas like the hippocampus and cortex, are essential for maintaining cognitive health. In AD, insulin signaling is disrupted, leading to reduced neuronal survival and synaptic function.

Current AD treatments focus on symptom relief rather than curing the disease. FDA-approved drugs include acetylcholinesterase inhibitors, NMDA receptor antagonists, and orexin receptor blockers. However, the development of disease-modifying therapies is slow, and many potential treatments are still under clinical investigation.

Alzheimer's disease is a complex and multifaceted disorder with significant impacts on individuals and society. Understanding the pathophysiology, especially the role of insulin resistance, is crucial for developing effective treatments. Current therapies provide symptom relief, but there is a pressing need for more research to find disease-modifying solutions.

REFERENCE:

Yoon JH, Hwang J, Son SU, Choi J, You SW, Park H, et al. How can insulin resistance cause Alzheimer’s disease? International Journal of Molecular Sciences [Internet]. 2023 Feb 9;24(4):3506. Available from: https://www.mdpi.com/1422-0067/24/4/3506

IMAGE REFERENCE:

https://www.frontiersin.org/files/Articles/417246/fnins-12-00830-HTML/image_m/fnins-12-00830-g001.jpg

https://en.m.wikipedia.org/wiki/File:Insulin_struct.png