Alzheimer’s Disease: The Great Morbidity of the 21st Century
Neuroangiogenesis (NAG) provides a vascular basis for understanding Alzheimer’s disease, senile dementias and cognitive decline with aging
The NAG hypothesis has two constructs: First, during aging there is a decline in capillary density due to waning neuroangiogenesis, which varies in different persons as determined by their genetic background. Second, this normal age-related decline may be accelerated by environmental factors depressing the usual levels of neuroangiogenic factors or may possibly be delayed by administration of exogenous angiogenic factors directly to the brain.
This hypothesis, if valid, has practical implications for preventing, reducing or possibly ameliorating Alzheimer’s disease and other senile dementias. Six therapeutic approaches have been discussed. In any future clinical studies, investigators will be challenged to determine the most effective and safest combination of neuroangiogenic factors to preserve or revive a healthy cerebral microcirculation.
On a lighter note, the mildest examples of a defective cerebral microcirculation may be those experienced by adults during casual conversations (“senior moments”) and by students during exam times, when perhaps several capillaries may be transiently compromised. Here I’m reminded of an old Sinatra song entitled “High Hopes,” about an ant who sought to topple a rubber tree plant. One chorus ends with “Oops, there goes another rubber tree plant.” When I can’t recall a familiar name or word, I now think to myself, “Oops, there goes another capillary in my brain.”
I must acknowledge here the countless investigators in this field whose contributions could not be cited in this short essay but provide silent support for the NAG hypothesis. I am greatly indebted to the Medical Center Library of the University of Kentucky and its expeditious staff member, Mrs. Amanda Williams. Finally, I acknowledge the long term support of the late Ch. Tray.
- Note: A more extensive list of references is available at American Scientist Online.
- Ambrose, C. T. 2010. The widening gyrus. American Scientist 98:270–274.
- Ambrose, C. T. 2012. Neuroangiogenesis: A vascular basis for Alzheimer’s disease and cognitive decline during aging. Journal of Alzheimer’s Disease 32:773–788.
- Callaway, E. 2012. Gene mutation defends against Alzheimer’s disease. Nature 487:153.
- Constanza, A., et al. 2011. Microvascular burden and Alzheimer-type lesions across the age spectrum. Journal of Alzheimer’s Disease 32:643–652.
- Dahm, R. 2010. Finding Alzheimer’s disease. American Scientist 98:148–155.
- Davies, C. A., et al. 1987. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease. Journal of Neurological Science 78:151–164.
- DeKosky, S. T., and S. W. Scheff. 1990. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: Correlation with cognitive severity. Annals of Neurology 27:457–464
- Eliezer, D. 2012. Visualizing amyloid assembly. Science 336:308–309.
- Markesbery, W. R. 1997. Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biology and Medicine 23:134–147.
- Nagele, R. G., et al. 2004. Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiology of Aging 25:663–674.
- Nelson, P. T., et al. 2011. Alzheimer’s disease is not “brain aging”; neuropathologic, genetic, and epidemiological human studies. Acta Neuropathologica, published online.
- Polidori, M., C. Pientka and P. Mecocci. 2011. A review of the major risk factors related to Alzheimer’s disease. Journal of Alzheimer’s Disease 32:521–530.
- Radnofsky, C. L. 2013. Americans die younger than peers. Wall Street Journal 10 January 2013, p. A2.
- Sanchez, A., et al. 2011. p38 MARK: a mediator of hypoxia-induced cerebrovascular inflammation. Journal of Alzheimer’s Disease 32:587–597.
- Zilboorg, G. 1942. A History of Medical Psychology. New York: W.W. Norton & Co., pp. 551–553.
- Zlokovic, B. V. 2005. Neurovascular mechanisms of Alzheimer’s neurodegeneration. TRENDS in Neuroscience 28:202–208.