Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias

The cortex of the brain is organized into clear horizontal layers, laminae, which subserve much of the connectional anatomy of the brain. We hypothesi ze that there is also a vertical anatomical organization that might subserv e local interactions of neuronal functional units, in accord with longstand ing electrophysiological observations. We develop and apply a general quant itative method, inspired by analogous methods in condensed matter physics, to examine the anatomical organization of the cortex in human brain. We fin d, in addition to obvious laminae, anatomical evidence for tightly packed m icrocolumnar ensembles containing approximately 11 neurons, with a periodic ity of about 80 mu m. We era mine the structural integrity of this new arch itectural feature in two common dementing illnesses, Alzheimer disease and dementia with Lewy bodies. In Alzheimer disease, there is a dramatic, nearl y complete loss of microcolumnar ensemble organization. The relative degree of loss of microcolumnar ensembles is directly proportional to the number of neurofibrillary tangles, but not related to the amount of amyloid-beta d eposition. In dementia with Lewy bodies, a similar disruption of microcolum nar ensemble architecture occurs despite minimal neuronal loss. These obser vations show that quantitative analysis of complex cortical architecture ca n be applied to analyze the anatomical basis of brain disorders.