Plasticity and the spread of Alzheimer's disease-like changes

Tangles are a major histopathological feature of Alzheimer's disease and their regional location and number correlate significantly with the individual's cognitive decline. Intriguingly, these tangles are formed only in a small subset of nerve cell types and are practically absent in most animal species examined so far. In humans, tangle formation seemingly starts decades before clinical signs of dementia are seen and spread over cortical areas in a regular manner described by the Braak classification. In the present article the role of plasticity-related molecules and mechanisms are discussed considering their putative role in neuronal vulnerability and spread of tangles. Special emphasis is given to some aspects of lipid metabolism, that is, apolipoprotein E polymorphism, statin effects, and lysosomal dysfunction in Alzheimer's and Niemann-Pick C's diseases.