Evolution of Alzheimer’s disease related cortical lesions

Abstract

Alzheimer’s disease is an immutably progressing dementing disorder. Its major pathologic hallmark is the gradual development of neurofibrillary changes in a few susceptible nerve cell types. The cortical changes do not occur inevitably with advancing age. Once the disease has begun, spontaneous recovery or remissions are not observed. The initial changes develop in poorly myelinated areas of the temporal lobe. The destructive process then follows a predictable pattern as it extends into other cortical areas. Advanced age is not a prerequisite for the evolution of the lesions. Alzheimer’s disease is thus an age-related, but not an age-dependent disease. The spread of the neurofibrillary changes resembles the process of cortical myelination, however in reverse order. The human cerebral cortex consists of a small allocortex and an extensive neocortex. The allocortex is located chiefly in the anteromedial portions of the temporal lobe and includes the hippocampal formation and the entorhinal region. The subcortical amygdala is closely related. The parietal, occipital, and temporal neocortices are each comprised of a primary core field, a secondary belt region, and related association areas. Sensory data proceeds through the core and belt fields to the respective association areas, and is then conveyed to the frontal association cortex (prefrontal cortex). Tracts generated in this highest organisational level of the human brain guide the data through the frontal belt (premotor areas) to the primary motor area. The striatal loop and the cerebellar loop provide the major routes for this transport. Part of the stream of data from the sensory association areas branches off and converges upon the entorhinal region and the amygdala (afferent leg of the limbic loop). The information is processed in the entorhinal region, amygdala, and hippocampal formation, and projections from all these areas contribute to the efferent leg of the limbic loop, which heads toward the prefrontal cortex (Fig. 1). All components of the limbic loop play a significant role in the maintenance of memory functions. Precisely these areas are susceptible to early and grave pathologic changes in Alzheimer’s disease (AD) (Kemper, 1978).