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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

Charles T. Ambrose


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.


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