Question: To what extent do lifestyle-related disorders like insulin resistance contribute to the development of Alzheimer’s disease?

Answer: Alzheimer’s disease (AD) is the most common type of dementia and is associated with the buildup of amyloid β deposits and neurofibrillary tangles, which interfere with cognitive function and motor control. On a cellular level, the condition is marked by the increased activation of death-related cellular signaling pathways, causing the physical infrastructure of the brain’s nervous system to deteriorate. Elucidating the cause of neurodegenerative decay has eluded scientists for decades. Rising cases of lifestyle-related, metabolic disorders like diabetes and obesity prompted researchers to investigate if there is a link between these lifestyle-related disorders and AD. Although Alzheimer’s disease is enigmatic and marked by a list of interconnected homeostatic abnormalities, studies from Brown University Medical School show links between diminished secretion of both insulin receptor and insulin-like growth factor I (IGF-I) in brain tissue and more severe cases of AD (Monte et al., 2005).

The scientists at Brown studied neural tissue mRNA and protein composition in deceased patients with early, middle, and late stage AD. Post-mortem frontal cortex tissue samples were collected and analyzed using real-time PCR to compare the expression of insulin, IGF-I, and IGF-II receptor protein. A correlation analysis indicated significantly reduced expression of the proteins in later stage AD patients (Steen et al., 2005).

Inadequate production of insulin signalling-pathway molecules is associated with insulin resistance, which is a hallmark of metabolic disorders such as diabetes and obesity. Hyperglycemia, or high blood sugar, may desensitize insulin receptors and hamper healthy energy metabolism in the cell. Statistically significant reductions in insulin receptor expression found in neurodegenerative brain tissues suggests the concurrence of AD with the development of insulin resistance. This data is correlative and thus does not indicate that insulin resistance causes AD., meaning more research is warranted; perhaps in the form of a longitudinal study in which insulin-resistant patients are monitored for AD development in old age vs non-insulin-resistant patients.

  • Joel S.

References:

  1. Monte, S. M. D. L., and Wands, J. R. (2008) Alzheimer’s Disease is Type 3 Diabetes–Evidence Reviewed. Journal of Diabetes Science and Technology. 2, 1101–1113.
  2. Steen, E., Tavares, R., Rivera, E. J., de la Monte, S. M., Cannon, J. L., and Neely, T. R. (2005) Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease – is this type 3 diabetes? Journal of Alzheimer’s Disease. 7, 63–80.
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