Where Alzheimer's starts and how it spreads

A new study involving 96 older adults initially free of dementia at the time of enrollment, of whom 12 subsequently developed mild Alzheimer’s, has clarified three fundamental issues about Alzheimer's: where it starts, why it starts there, and how it spreads.

Specifically, it begins in the lateral entorhinal cortex (LEC), a gateway to the hippocampus. Over time, Alzheimer's spreads from the LEC directly to other areas of the cerebral cortex, in particular the parietal cortex. It’s thought that it spreads by compromising the function of neurons in the LEC, which then compromises the integrity of neurons in adjoining areas.

Mouse models comparing the effects of elevated levels of tau in the LEC with elevated levels of APP, and with elevated levels of both, found that LEC dysfunction occurred only in the mice with high levels of both tau and APP. The LEC normally accumulates tau, making it more vulnerable to the accumulation of APP.


[3582] Khan UA, Liu L, Provenzano FA, Berman DE, Profaci CP, Sloan R, Mayeux R, Duff KE, Small SA. Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease. Nature Neuroscience [Internet]. 2014 ;17(2):304 - 311. Available from: http://www.nature.com/neuro/journal/v17/n2/full/nn.3606.html