title: Plasticity and neurotransmitter receptor changes in Alzheimer's disease and experimental cortical infarcts.
abstract: According to recently published data, the propagation of the typical neurofibrillary changes in Alzheimer's disease follows gradually and systematically the main pathways of fiber connections between different cortical areas. The functional deficits show a parallel development. Memory deficits as the first symptom of Alzheimer's disease can be explained by the initial lesion of the entorhinal-hippocampal connection. The next symptom is the impairment of emotional behaviour, which is caused by lesions in the hippocampus and the other parts of the limbic cortex. The following gnostic and praxic alterations can be explained by lesions in the association areas of the neocortex. Finally also motor disturbances become apparent, caused by lesions in the motor cortex. The tissue alterations in Alzheimer's disease represent a systemically spreading lesion in the cortex based on the destruction of synapses and finally of whole neurons, and on the impairment of normal neurotransmission. Since neurotransmission depends on transmitters and their receptors, the densities of transmitter receptors in the hippocampus, parietal association and premotor cortices in Alzheimer's disease were measured with quantitative receptor autoradiography. The degree of receptor changes in these regions decreases with the direction of the propagation of neurofibrillary changes from the hippocampus to the premotor cortex. With the exception of the GABAA receptor, the receptors in the hippocampus are reduced by approximately 70%. The reduction in the parietal association cortex amounts to only 30%. An upregulation of muscarinic M1 receptors was seen in the premotor cortex. The latter result is surprising in the context of a lesion model, but is in agreement with earlier immunohistochemical data about muscarinic receptors in the frontal cortex of Alzheimer patients.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: C. & O. Vogt Institute of Brain Research, Heinrich-Heine-University, Düsseldorf, Fed. Rep. of Germany.
authors.forename: K
authors.initials: K
authors.lastname: Zilles
authors.forename: M
authors.initials: M
authors.lastname: Qü
authors.forename: A
authors.initials: A
authors.lastname: Schleicher
authors.forename: M
authors.initials: M
authors.lastname: Schroeter
authors.forename: M
authors.initials: M
authors.lastname: Kraemer
authors.forename: O W
authors.initials: OW
authors.lastname: Witte
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001345:Autoradiography; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007051:Ibotenic Acid; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid