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Future Neurol. 2012 Sep;7(5):557-571.

Malignant synaptic growth and Alzheimer's disease.

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Center for Memory & Brain, Boston University, 2 Cummington St, Boston, MA 02215, USA.


In this article, we will describe the malignant synaptic growth hypothesis of Alzheimer's disease. Originally presented in 1994, the hypothesis remains a viable model of the functional and biophysical mechanisms underlying the development and progression of Alzheimer's disease. In this article, we will refresh the model with references to relevant empirical support that has been generated in the intervening two decades since it's original presentation. We will include discussion of its relationship, in terms of points of alignment and points of contention, to other models of Alzheimer's disease, including the cholinergic hypothesis and the tau and β-amyloid models of Alzheimer's disease. Finally, we propose several falsifiable predictions made by the malignant synaptic growth hypothesis and describe the avenues of treatment that hold the greatest promise under this hypothesis.


Alzheimer’s; acetylcholine; computational model; dementia; excitotoxicity; long-term potentiation; neurofibrillary tangles; plasticity; tau; β amyloid

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