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A study on the mass lesion effect of senile plaques
122A
Dementia
BIOL PSYCH'-,TRY 1991;29:43A- 185A
168 PROTON (IH) NMR STUDIES OF AMINO ACIDS IN ALZHEIMER'S DISEASE BRAIN W.E. Klunk, M.D., Ph.D., K. Panchalingam, Ph.D., R.J. McClure, Ph.D., J.W. Pettegrew, M.D. Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213. Previous .~tp NMR studies have shown alterations in membrane phosphulipid and energy metabolism in Alzheimer's disease (AD) brain. Since only phosphorus-containing metabolites can be studied with this method, we have begun to examine water-soluble (perchloric acid) and lipid-soluble (Folch) extracts by ~H NMR spectroscopy. ~H NMR spectroscopy has the advantage of being able to assess many more metabolites since .,dmost all compounds of interest will contain some protons. Extracts of eight brains with autopsy° verified AD and four age-matched control brains have been studied. The IH NMR resonances of these extracts have been largely identified by one- and two-dimensional IH NMR spectroscopy and pH conditions have been optimized for separating resonances of interest. These include the putative neuronal marker, Nacetyl-aspartate (NAA), glutamate, glutamine, GABA, taurine, and aspartate. NAA decreases in AD as the numbers of senile plaques increase, supporting a role for NAA as an in vitro and in vivo neuronal marker. Glutamate and glutamine increase with the number of senile plaques, suggesting that the relative amount of excitatory neurotransmitter per neuron ~reases as AD progresses. These relative changes may be more important than absolute changes and may play a role in neuronal death in AD. These in vitro studies will lay a foundation for future studies of AD by in vivo ~H NMR spectroscopy.
169 A STUDY ON THE MASS LESION EFFECT OF SENILE PLAQUES Manuel F. Casanova, M.D., Kunimasa Arima, M.D., Joel E. Kleinman, M.D., Ph.D. NIMH Neuroscience Center at St. Elizabeths, Washington. D.C. 20032. Ever since the turn of the century multiple studies have suggested that clinical deterioration in Alzheimer's disease (AD) is accompanied by a gradual increase in both the size and n,imbers of senile plaques (SPs). In the present study we investigated whether the "'mass effect" of SPs aifertoi the morphometry of adjacent neurons. For this purpose pyramidal cells from the hippocampus of eight AD patien!~. IO schizophrenic (SC) patients, and five cognitively impaired non-AD non-SC control patients were studied with a computerized image analysis system. Software routines allowed for the calculation of cell shape, area and disarray. An X-Y plotter quantitated the number of SPs and neurofibrillary tangles (NFTs) per corpus ammonis subfield. Our results indicated no significant differences between groups for measurements of neuronal size, disarray or shape. Contrary to previous reports, no evidence of pyramidal cell disarray was noted in schizophrenic patients. Our results suggest that SPs behave as inert structures with no evidence of mass effect on their surrounding neurons.
POSTER SESSION DEMENTIA F r i d a y , M a y 10, 1 : 0 0 - 6 : 0 0 PM
PonchartrainA
170 CORTISOL SECRETION AND AD PROGRESSION Myron F. Weiner, M.D. Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75235.
Dementia
BIOL PSYCH'-,TRY 1991;29:43A- 185A
168 PROTON (IH) NMR STUDIES OF AMINO ACIDS IN ALZHEIMER'S DISEASE BRAIN W.E. Klunk, M.D., Ph.D., K. Panchalingam, Ph.D., R.J. McClure, Ph.D., J.W. Pettegrew, M.D. Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213. Previous .~tp NMR studies have shown alterations in membrane phosphulipid and energy metabolism in Alzheimer's disease (AD) brain. Since only phosphorus-containing metabolites can be studied with this method, we have begun to examine water-soluble (perchloric acid) and lipid-soluble (Folch) extracts by ~H NMR spectroscopy. ~H NMR spectroscopy has the advantage of being able to assess many more metabolites since .,dmost all compounds of interest will contain some protons. Extracts of eight brains with autopsy° verified AD and four age-matched control brains have been studied. The IH NMR resonances of these extracts have been largely identified by one- and two-dimensional IH NMR spectroscopy and pH conditions have been optimized for separating resonances of interest. These include the putative neuronal marker, Nacetyl-aspartate (NAA), glutamate, glutamine, GABA, taurine, and aspartate. NAA decreases in AD as the numbers of senile plaques increase, supporting a role for NAA as an in vitro and in vivo neuronal marker. Glutamate and glutamine increase with the number of senile plaques, suggesting that the relative amount of excitatory neurotransmitter per neuron ~reases as AD progresses. These relative changes may be more important than absolute changes and may play a role in neuronal death in AD. These in vitro studies will lay a foundation for future studies of AD by in vivo ~H NMR spectroscopy.
169 A STUDY ON THE MASS LESION EFFECT OF SENILE PLAQUES Manuel F. Casanova, M.D., Kunimasa Arima, M.D., Joel E. Kleinman, M.D., Ph.D. NIMH Neuroscience Center at St. Elizabeths, Washington. D.C. 20032. Ever since the turn of the century multiple studies have suggested that clinical deterioration in Alzheimer's disease (AD) is accompanied by a gradual increase in both the size and n,imbers of senile plaques (SPs). In the present study we investigated whether the "'mass effect" of SPs aifertoi the morphometry of adjacent neurons. For this purpose pyramidal cells from the hippocampus of eight AD patien!~. IO schizophrenic (SC) patients, and five cognitively impaired non-AD non-SC control patients were studied with a computerized image analysis system. Software routines allowed for the calculation of cell shape, area and disarray. An X-Y plotter quantitated the number of SPs and neurofibrillary tangles (NFTs) per corpus ammonis subfield. Our results indicated no significant differences between groups for measurements of neuronal size, disarray or shape. Contrary to previous reports, no evidence of pyramidal cell disarray was noted in schizophrenic patients. Our results suggest that SPs behave as inert structures with no evidence of mass effect on their surrounding neurons.
POSTER SESSION DEMENTIA F r i d a y , M a y 10, 1 : 0 0 - 6 : 0 0 PM
PonchartrainA
170 CORTISOL SECRETION AND AD PROGRESSION Myron F. Weiner, M.D. Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75235.