Hypotheses and Dynamics in the Pathogenesis of Neurodegenerative Disorders

Estrogens, particularly estradiol-beta, constitute a complexity in hormonereceptivity that evolves via the prevention of delayed cell-death pathways. Neurodegeneration, and ischemic injury to neural tissue, represent a panoramic array of effects that are especially linked to physiologic levels of estradiol-beta. The aging brain, in particular, involves the developmental emergence of immediate gene response that is linked to such estrogen-receptor interactions.

The various dimensional attributes of an actively progressive neurodegenerative process closely resembles the evolutionary dynamics of a predetermined cascade that is defined as pathway endresult. It is significant to view the different contrasting processes as events individually evolving in terms of either neuronal depletion or pathway interruption. It would appear that onset events are attributable to a predetermination that self-promotes the initial steps in defining such neurodegeneration.

Strict evolutionary principles would apply for the pathogenesis of both local and global pathway events in delineating lesions of Alzheimer type. It is further to be realized that the complex modulatory role of disease activity conforms to the advancement and propagation of a substrate susceptibility indicative of further cascade events in such evolution. Overall dimensions of expansion and contraction would perhaps account for the betaamyloid turnover events between the intracellular and extracellular compartments in a manner specifically inducive towards a complex constitution of atrophy and neuronal loss in the cerebral cortex. Synaptic compromise and the post-synaptic receptor apparatus would further indicate the development of subsidiary or secondary pathways that include a significant role for plasticity in lesion involvement.

Etiology and pathogenesis of dementing illness is largely resolvable in terms of consequences of an advancing age that promotes the actual progression as assessed by the sequential development of lesions cardinal to the neuronal circuitry involvement. One might view the dynamics of such sequences as a contributing role in the actual evolution of lesions that centrally manifest as neuronal pathophysiology. It is only in terms beyond the actual neuropathologic lesions that an endstage consequence is dominated by irreversible transforming features in the transport mechanics of both injury and compensation of neuronal function.

Relative attempts at modulation and manipulative processing of neurotransmitter release and receptivity at the post-synaptic membrane appear central to the consequences of synaptic loss in Alzheimer’s disease. In view of the ongoing dynamics of further injury to neurons in this disorder, it would perhaps prove important to recognize consequences of disease as themselves pathogenic targets in the evolutionary definition of further injury as progression, particularly in terms of both neuronal cell and synapse loss.

Integral constitutional events in neurofibrillary degeneration relate particularly to the multiphosphorylation sites that discretely segregate molecules in a loosely bound structure present intraneuronally. It is significant that neurofibrillary tangles correspond to spread of disease involvement in Alzheimer brains. It would further appear that the further progression of these lesions would significantly constitute a variable correlate of the senile plaque load.

Vascular lesions compound effects on the clinical demented state in patients with Alzheimer disease [122]. A given degree of dementia in Alzheimer disease patients suffering from concomitant ischemic lesions in the cerebrum is associated with lesser numbers of neurofibrillary tangles and neuritic plaques. This synergistic effect of ischemic lesions with cognitive decline in Alzheimer patients correlates also with the presence often of congophilic angiopathy. A particular aspect of ischemic lesions is the association of Alzheimer disease in patients with biochemical markers for cerebrovascular disease.

Vascular lesions compound effects on the clinical demented state in patients with Alzheimer disease [122]. A given degree of dementia in Alzheimer disease patients suffering from concomitant ischemic lesions in the cerebrum is associated with lesser numbers of neurofibrillary tangles and neuritic plaques. This synergistic effect of ischemic lesions with cognitive decline in Alzheimer patients correlates also with the presence often of congophilic angiopathy. A particular aspect of ischemic lesions is the association of Alzheimer disease in patients with biochemical markers for cerebrovascular disease.