Abstract: It would appear that pathways of impaired autophagy are inherently conducive to co-localization of neurofilaments, with the formation of neurofibrillary tangles and with synapse loss. Indeed, intracytoplasmic amyloidogenesis might, in specific ways, be a component system in production of both synapse loss and neuronal cell death largely in terms of the etiologic cause of the amyloidogenesis as a prototype of cellular degeneration in its own right. It might perhaps be relevant to consider how synapse loss and neuronal cell death would implicate reactivity of lysosomes that affects the metabolic activity of neurons. A low neuronal metabolic rate would inherently affect trafficking systems and also the production of a variable response to different insults ranging from neurotrophin factor lack to ischemia primarily evolving as phenomena centered on cerebral cortical neurons. Impaired autophagy implicating abnormal lysosomal activation would promote the accumulation of ubiquinated endproducts of neuronal metabolism with the appearance of phosphorylated neurofilament aggregates and granulovacuolar degeneration. Interpretative assessment of neuronal inclusion body phenomena in selected neuronal subsets might implicate a failed central pathway mechanism promoting the development of neurodegeneration. Indeed, it is in terms of primary lysosomal disease that major neuropathologic lesions in Alzheimer`s disease would be conducive to subsequent slowly progressive neurodegeneration as a selective neuronal subset phenomenon. It might be significant to recognize amyloidogenesis as a reflected consequence of such lysosomal involvement beyond simple considerations of directly involved proapoptosis or cell cyclical activity but within a strict context of impaired turnover events affecting cell organelles in particular.