“My review article provides food for thought and action for scientists and clinicians interested in AD.”

Alzheimer's disease (AD) is a devastating age-related disorder of progressive memory impairment and behavioral disturbances that exacts a toll not only on the patient, but also on his/her family and friends. Rapid advances on multiple fronts—genetics, cell and molecular biology, brain imaging, and epidemiology, among others—have revealed some of the major abnormalities that result in the dysfunction of synapses and the death of neurons in AD. This paper is highly cited because it is a review article that describes the current state of knowledge of the cellular and molecular mechanisms of AD in the context of genes, aging, and the environment. I attempted to write the article so that it was concise and readable, yet inclusive of a range of findings and issues concerning the cellular and molecular mechanisms of neuronal dysfunction and death in AD, and preventative and therapeutic approaches that have/will emerge from this research. The history of AD research is a wonderful example of how studying a disease can reveal previously unrecognized physiological mechanisms, with the story of the secretases that cleave the amyloid precursor protein and Notch1 being a prime example. Human Notch1 is a modular, single-pass transmembrane receptor that normally controls cellular differentiation in hematopoetic including neurons. The complexity of this disease encompasses an increasing number of disciplines, including free-radical biology, regulation of cellular ion homeostasis and energy metabolism, and immunology. My review article provides food for thought and action for scientists and clinicians interested in AD.

• - Read an interview with Mark Mattson in Science Watch^®.
     
• View the special topic of Alzheimer's disease.