Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease

Senile (neuritic) plaques are one of the two major neuropathologic hallmarks of Alzheimer's disease. Despite their obvious importance (e.g., they are significantly correlated with severity of dementia), there is little present information about their etiology, the specific neuronal elements that form them, or a quantitative definition of where in cortex they occur. We have sought clues to these issues by quantifying regional and laminar distributions of neocortical plaques and setting these data against the present wealth of information on neocortical cytoarchitecture and neurotransmitter-specific circuitry. Senile plaques are significantly more numerous in associative regions of neocortex than in sensory areas and are significantly more numerous in cortical laminae dominated by their role in corticocortical, associative relations. Plaques are also largest in those laminae characterized by large pyramidal cells subserving input/output functions. The quantitative distribution of senile plaques in Alzheimer's disease does not necessarily correspond to innervation patterns for any known subcortical afferent system. This, coupled with the finding that several different neurotransmitters can be immunocytochemically co-localized with plaques, casts doubts on a primary role of cholinergic deterioration in plaque etiology, and opens the possibility that neocortical senile plaques may derive from pathologic events initiated in the neocortex.