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809 results on '"Ikonomovic, Milos"'

203. IC-P-163: In vivo amyloid deposition and neuropathological findings after humanized amyloid β-specific monoclonal antibodies therapy in a patient with Alzheimer's disease

Author

Lopez, Oscar L., primary, Hamilton, Ronald, additional, Ikonomovic, Milos, additional, Mathis, Chester A., additional, Price, Julie A., additional, Becker, James T., additional, Saxton, Judith A., additional, DeKosky, Steven T., additional, and Klunk, William E., additional

Published
2009
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207. Postmortem neocortical 3H‐PiB binding and levels of unmodified and pyroglutamate Aβ in Down syndrome and sporadic Alzheimer's disease.

Author

Pivtoraiko, Violetta, Racic, Tamara, Abrahamson, Eric E, Villemagne, Victor L, Handen, Benjamin L, Lott, Ira T, Head, Elizabeth, and Ikonomovic, Milos D

Abstract

Background: Individuals with Down syndrome (DS) have a genetic predisposition for amyloid‐β (Aβ) overproduction and earlier onset of Aβ deposits compared to sporadic late‐onset Alzheimer's disease (AD). Positron emission tomography (PET) with Pittsburgh Compound‐B (PiB) detects fibrillar Aβ pathology in living people with DS and AD, but its relationship with heterogeneous Aβ forms aggregated within amyloid deposits is not well understood. Method: We performed quantitative in‐vitro 3H‐PiB binding assays and enzyme‐linked immunosorbent assays of fibrillar (insoluble) unmodified Aβ40 and Aβ42 forms and N‐terminus truncated and pyroglutamate‐modified AβNpE3‐40 and AβNpE3‐42 forms in postmortem frontal cortex and precuneus samples from 18 DS cases aged 43‐63 years and 17 late‐onset AD cases aged 62‐99 years. Result: Compared to the AD group, the DS group had higher levels of Aβ40 and AβNpE3‐40, while the two groups did not differ by Aβ42 and AβNpE3‐42 levels, in both the frontal cortex and precuneus. This resulted in lower ratios of Aβ42/Aβ40 and AβNpE3‐42/AβNpE3‐40 in the DS group compared to the AD group, in both cortical regions. Correlations of Aβ42/Aβ40 and AβNpE3‐42/AβNpE3‐40 ratios with CAA severity were strong in DS cases, and weak in AD cases. The two diagnostic groups did not differ significantly by 3H‐PiB binding levels in the frontal cortex or in the precuneus. Conclusion: These results demonstrate that compared to late‐onset AD cases, adult DS individuals with similar burden of cortical Aβ plaques have a preponderance of both pyroglutamate‐modified AβNpE3‐40 and unmodified Aβ40 forms which are associated with greater CAA pathology. Despite the distinct molecular profile of Aβ forms and greater vascular amyloidosis in DS cases, cortical 3H‐PiB binding does not distinguish between diagnostic groups that are at an advanced level of amyloid plaque pathology. These results underscore the need for development of CAA‐selective PET radiopharmaceuticals in order to detect and track the progression of cerebral vascular amyloid deposits in relation to Aβ plaques at the earliest pathology stages in individuals with DS. [ABSTRACT FROM AUTHOR]

Published
2022
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211. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease

Author

Ikonomovic, Milos D., primary, Klunk, William E., additional, Abrahamson, Eric E., additional, Mathis, Chester A., additional, Price, Julie C., additional, Tsopelas, Nicholas D., additional, Lopresti, Brian J., additional, Ziolko, Scott, additional, Bi, Wenzhu, additional, Paljug, William R., additional, Debnath, Manik L., additional, Hope, Caroline E., additional, Isanski, Barbara A., additional, Hamilton, Ronald L., additional, and DeKosky, Steven T., additional

Published
2008
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215. P-029: Correlation of regional in VIVO pittsburgh compound-B (PIB) retention with in vitro PIB, Aβ levels, and amyloid plaque density: Validation of PIB-PET in postmortem human brain

Author

DeKosky, Steven Trent, primary, Mathis, Chet A., additional, Price, Julie C., additional, Ikonomovic, Milos D., additional, Hamilton, Ronald L., additional, Abrahamson, Eric E., additional, Paljug, Willam R., additional, Debnath, Manik L., additional, Hope, Caroline E., additional, Isanski, Barbara A., additional, Tsopelas, Nikolaos D., additional, Lopresti, Brian J., additional, Ziolko, Scott, additional, Bi, Wehzu, additional, and Klunk, William E., additional

Published
2007
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217. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue.

Author

Marquié, Marta, Normandin, Marc D., Vanderburg, Charles R., Costantino, Isabel M., Bien, Elizabeth A., Rycyna, Lisa G., Klunk, William E., Mathis, Chester A., Ikonomovic, Milos D., Debnath, Manik L., Vasdev, Neil, Dickerson, Bradford C., Gomperts, Stephen N., Growdon, John H., Johnson, Keith A., Frosch, Matthew P., Hyman, Bradley T., and Gómez‐Isla, Teresa

Subjects
BRAIN, PROTEIN metabolism, ALZHEIMER'S disease, CEREBRAL hemorrhage, CELLS, DEAD, DEMENTIA, NERVE tissue proteins, NEURODEGENERATION, PYRIDINE, RADIOGRAPHY, RADIOPHARMACEUTICALS, RESEARCH funding, POSITRON emission tomography, FRONTOTEMPORAL lobar degeneration, TDP-43 proteinopathies
Abstract

Objective: To examine region- and substrate-specific autoradiographic and in vitro binding patterns of positron emission tomography tracer [F-18]-AV-1451 (previously known as T807), tailored to allow in vivo detection of paired helical filament-tau-containing lesions, and to determine whether there is off-target binding to other amyloid/non-amyloid proteins.Methods: We applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography, and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau, frontotemporal lobar degeneration-transactive response DNA binding protein 43 (TDP-43), progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology.Results: Our data suggest that [F-18]-AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer brains (eg, intraneuronal and extraneuronal tangles and dystrophic neurites), but does not seem to bind to a significant extent to neuronal and glial inclusions mainly composed of straight tau filaments in non-Alzheimer tauopathy brains or to lesions containing β-amyloid, α-synuclein, or TDP-43. [F-18]-AV-1451 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions was identified.Interpretation: Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention. [ABSTRACT FROM AUTHOR]

Published
2015
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219. Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease.

Author

Scheff, Stephen W., Price, Douglas A., Ansari, Mubeen A., Roberts, Kelly N., Schmitt, Frederick A., Ikonomovic, Milos D., and Mufson, Elliott J.

Subjects
ALZHEIMER'S disease research, DISEASE progression, BRAIN diseases, SYNAPSES, BRAIN imaging
Abstract

Mild cognitive impairment (MCI) is considered to be an early stage in the progression of Alzheimer's disease (AD) providing an opportunity to investigate brain pathogenesis prior to the onset of dementia. Neuroimaging studies have identified the posterior cingulate gyrus (PostC) as a cortical region affected early in the onset of AD. This association cortex is involved in a variety of different cognitive tasks and is intimately connected with the hippocampal/entorhinal cortex region, a component of the medial temporal memory circuit that displays early AD pathology. We quantified the total number of synapses in lamina 3 of the PostC using unbiased stereology coupled with electron microscopy from short postmortem autopsy tissue harvested from cases at different stage of AD progression. Individuals in the early stages of AD showed a significant decline in synaptic numbers compared to individuals with no cognitive impairment (NCI). Subjects with MCI exhibited synaptic numbers that were between the AD and NCI cohorts. Adjacent tissue was evaluated for changes in both pre and postsynaptic proteins levels. Individuals with MCI demonstrated a significant loss in presynaptic markers synapsin-1 and synaptophysin and postsynaptic markers PSD-95 and SAP-97. Levels of [3H]PiB binding was significantly increased in MCI and AD and correlated strongly with levels of synaptic proteins. All synaptic markers showed a significant association with Mini-Mental Status Examination scores. These results support the idea that the PostC synaptic function is affected during the prodromal stage of the disease and may underlie some of the early clinical sequelae associated with AD. [ABSTRACT FROM AUTHOR]

Published
2015
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223. Binding of the Positron Emission Tomography Tracer Pittsburgh Compound-B Reflects the Amount of Amyloid-β in Alzheimer's Disease Brain But Not in Transgenic Mouse Brain

Author

Klunk, William E., primary, Lopresti, Brian J., additional, Ikonomovic, Milos D., additional, Lefterov, Iliya M., additional, Koldamova, Radosveta P., additional, Abrahamson, Eric E., additional, Debnath, Manik L., additional, Holt, Daniel P., additional, Huang, Guo-feng, additional, Shao, Li, additional, DeKosky, Steven T., additional, Price, Julie C., additional, and Mathis, Chester A., additional

Published
2005
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228. [P-130]: Binding of the amyloid-imaging PET tracer, Pittsburgh Compound-B, to post-mortem human brain tissue from the AN-1792 immunotherapy trial

Author

Klunk, William E., primary, Ikonomovic, Milos D., additional, Masliah, Eliezer, additional, Ferrer, Isidro, additional, Kirby, Louis C., additional, Price, Julie C., additional, Abrahamson, Eric E., additional, Paljug, William R., additional, Mathis, Chester A., additional, and DeKosky, Steven T., additional

Published
2005
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235. P2-031 Amyloid deposits in transgenic PS1/APP mice do not bind the amyloid pet tracer, PIB, in the same manner as human brain amyloid

Author

Klunk, William E., primary, Lopresti, Brian J., additional, Debnath, Manik L., additional, Holt, Daniel P., additional, Wang, Yanning, additional, Huang, Guo-feng, additional, Shao, Li, additional, Lefterov, Iliya, additional, Koldamova, Radosteva, additional, Ikonomovic, Milos, additional, DeKosky, Steven T., additional, and Mathis, Chester A., additional

Published
2004
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242. COMPARATIVE ANALYSIS OF PIB IN VIVO WITH 6-CN-PIB AND Aβ-IMMUNOHISTOCHEMISTRY POSTMORTEM IN FAMILIAL ALZHEIMER DISEASE ASSOCIATED WITH THE PSEN1 I229F MUTATION

Author

Ghetti, Bernardino Francesco, Newell, Kathy L., Abrahamson, Eric E., Cairns, Nigel J., Murrell, Jill R., Oblak, Adrian L., Unverzagt, Frederick W., Farlow, Martin Rhys, Epperson, Francine, Richardson, Rose, Dupree, Brenda, Morris, John C., Klunk, William Edward, Saykin, Andrew J., Risacher, Shannon Leigh, and Ikonomovic, Milos D.

Published
2014
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243. Plasma and cerebrospinal fluid α1‐antichymotrypsin levels in Alzheimer's disease: Correlation with cognitive impairment

Author

DeKosky, Steven T., primary, Ikonomovic, Milos D., additional, Wang, Xiaoyan, additional, Farlow, Martin, additional, Wisniewski, Stephen, additional, Lopez, Oscar L., additional, Becker, James T., additional, Saxton, Judith, additional, Klunk, William E., additional, Sweet, Robert, additional, Kaufer, Daniel I., additional, and Kamboh, M. Ilyas, additional

Published
2002
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246. Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease*

Author

Sweet, Robert A., MacDonald, Matthew L., Kirkwood, Caitlin M., Ding, Ying, Schempf, Tadhg, Jones-Laughner, Jackie, Kofler, Julia, Ikonomovic, Milos D., Lopez, Oscar L., Garver, Megan E., Fitz, Nicholas F., Koldamova, Radosveta, and Yates, Nathan A.

Abstract

It has been hypothesized that Alzheimer disease (AD) is primarily a disorder of the synapse. However, assessment of the synaptic proteome in AD subjects has been limited to a small number of proteins and often included subjects with end-stage pathology. Protein from prefrontal cortex gray matter of 59 AD subjects with mild to moderate dementia and 12 normal elderly subjects was assayed using targeted mass spectrometry to quantify 191 synaptically expressed proteins. The profile of synaptic protein expression clustered AD subjects into two groups. One of these was characterized by reduced expression of glutamate receptor proteins, significantly increased synaptic protein network coexpression, and associated withApolipoprotein E*4 (APOE*4) carrier status. The second group, by contrast, showed few differences from control subjects. A subset of AD subjects had altered prefrontal cortex synaptic proteostasis for glutamate receptors and their signaling partners. Efforts to therapeutically target glutamate receptors in AD may have outcomes dependent on APOE*4 genotype.

Published
2016
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247. Effects of Maternal Choline Supplementation on the Septohippocampal Cholinergic System in the Ts65Dn Mouse Model of Down Syndrome

Author

M. Kelley, Christy, A. Ash, Jessica, E. Powers, Brian, Velazquez, Ramon, J. Alldred, Melissa, D. Ikonomovic, Milos, D. Ginsberg, Stephen, J. Strupp, Barbara, and J. Mufson, Elliott

Abstract

Down syndrome (DS), caused by trisomy of chromosome 21, is marked by intellectual disability (ID) and early onset of Alzheimer’s disease (AD) neuropathology including hippocampal cholinergic projection system degeneration. Here we determined the effects of age and maternal choline supplementation (MCS) on hippocampal cholinergic deficits in Ts65Dn mice compared to 2N mice sacrificed at 6-8 and 14-18 months of age. Ts65Dn mice and disomic (2N) littermates sacrificed at ages 6-8 and 14-18 mos were used for an aging study and Ts65Dn and 2N mice derived from Ts65Dn dams were maintained on either a choline-supplemented or a choline-controlled diet (conception to weaning) and examined at 14-18 mos for MCS studies. In the latter, mice were behaviorally tested on the radial arm Morris water maze (RAWM) and hippocampal tissue was examined for intensity of choline acetyltransferase (ChAT) immunoreactivity. Hippocampal ChAT activity was evaluated in a separate cohort. ChAT-positive fiber innervation was significantly higher in the hippocampus and dentate gyrus in Ts65Dn mice compared with 2N mice, independent of age or maternal diet. Similarly, hippocampal ChAT activity was significantly elevated in Ts65Dn mice compared to 2N mice, independent of maternal diet. A significant increase with age was seen in hippocampal cholinergic innervation of 2N mice, but not Ts65Dn mice. Degree of ChAT intensity correlated negatively with spatial memory ability in unsupplemented 2N and Ts65Dn mice, but positively in MCS 2N mice. The increased innervation produced by MCS appears to improve hippocampal function, making this a therapy that may be exploited for future translational approaches in human DS.

Published
2016

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