Pathogenetic Determination of Selective Vulnerability of Subcellular Neuronal Membranes in Age-Related Dementia

Organic demented states would evolve as patterns of neuronal susceptibility in terms primarily of subcellular or organelle injury. Neurofibrillary tangle formation and neuritic plaque deposition would be associated with amyloidogenesis that progresses largely as a consequence of oxidative stress. Disrupted neuronal circuits might, in real terms, constitute operative mechanistic expression and progression of the demented state that is inherently age-related and that arises as oxidative stress-related phenomena. Interactive pathways of neurodegeneration would perhaps promote the development of constitutional frameworks of Alzheimer-type pathogenesis as individual neuronal and especially as subcellular components, of integral neuronal circuits. Oxidative stress would evolve in terms of a susceptibility of neurons that permits definition of neuronal network dysfunction beyond just individual neuronal cellular pathways. Abnormal synaptogenesis and dendritic dystrophy would arise both in relation to oxidative stress and also to evolving cellular organelle damage that further characterizes the selectivity of neuronal vulnerability. Indeed, it is perhaps in terms especially of ongoing oxidative stress to cellular membrane components that neurons would constitute a primary target in age-related dementia and as Alzheimer-type pathobiology.