Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease.

Abstract

The numbers and distribution of the neurofibrillary tangles and neuritic plaques have been determined in several areas of the neocortex in brains affected by various degrees of severity of Alzheimer disease. The homotypical cortex of the "association" areas of the temporal, parietal, and frontal lobes are severely involved, whereas the motor, somatic sensory, and primary visual areas are virtually unaffected. The neurofibrillary tangles are mainly in the supra-and infragranular layers, particularly in layers Ill and V. In all areas except area 18 in the occipital lobe, there are approximately twice as many tangles in layer V as in layer III. The tangles are arranged in definite clusters, and those in the supra-and infragranular layers are in register. The neuritic plaques occur in all layers but predominantly affect layers II and Ill and do not show clustering. These data on the severity of the pathological involvement in different areas of the neocortex and the laminar distribution and the clustering of the tangles support the suggestion that the pathological changes in Alzheimer disease affect regions that are interconnected by well-defined groups of connections and that the disease process may extend along the connecting fibers. The invariable and severe involvement of the olfactory areas of the brain in this disease is in striking contrast to the minimal changes in the somatic sensory and primary visual areas and raises the possibility that the olfactory pathway may be initially involved.

Patterns of cortical activity and memory performance in Alzheimer’s disease

“…Neuropathologic studies in AD (Pearson et al 1985) indicate maximal involvement of association areas and minimal involvement of primary sensory areas. However, an ophthalmologic study found evidence for a widespread visual dysfunction in AD (Cronin-Golomb et al 1991).…”

Targeting Axonal Protein Synthesis in Neuroregeneration and Degeneration

“…The locally synthesized ATF4 is retrogradely transported in a dynein-dependent manner to the neuronal cell bodies, ATF4 levels and ATF4-dependent transcription in the neuronal soma increase, and ATF4-dependent expression of CCAATenhancer-binding protein homologous protein (CHOP) is upregulated leading to cell death. Pathological changes in AD spread through the brain in a nonrandom manner that indicates propagation along connecting fiber tracts [57]. The molecular mechanisms driving the spread of pathology remain largely unknown.…”

Two aspects of impaired consciousness in Alzheimer's disease

“…Thus, loss of synaptic contacts in associative cortices and limbic structures would interrupt long connecting pathways in AD (Hyman et al, 1984;Pearson et al, 1985). The relative preservation of automatic processes in AD patients would mean that these processes are subserved by circumscribed cortical areas that are less affected by disconnection in the early stages of the disease.…”