Subtle changes in the ageing human brain.

Subtle changes in the human brain constitute a third element in addition to plaques and tangles as markers of vulnerability to Alzheimer's disease (AD). Neurofibrillary tangle (NFT) distribution shows the closest relationship to the severity of dementia. Two features of the distribution (regional selectivity and columnar clustering) provide clues about the structural changes due to normal ageing that may precede tangle formation. It is hypothesized that the columnar organization of the cortex, determines the pattern of pathological spread in AD and, consequently, the pattern of function loss. Minicolum thinning occurs in normal ageing and echoes the selective regional distribution of NFT formation in AD. NFT vulnerability appears to emerge from hierarchical variation in neural plasticity associated with the hierarchical variation in size and spacing of mini and macro-columns in the cortex. Regional differences may involve regional variation in gene expression. Dietary Omega 3 fatty acid intake has been shown to have neuroprotective effects on the cytoarchitectural features that contribute to this cortical hierarchy