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Article: AMYLOID CLEARING IMMUNOTHERAPY FOR ALZHEIMER'S DISEASE AND THE RISK OF CEREBRAL AMYLOID ANGIOPATHY.

Kile, Shawn J / Olichney, John M

Alzheimer's disease research journal

2014 Volume 1, Issue 1-2, Page(s) 5–12

Abstract: Immunization strategies which aid in the clearance of beta-amyloid (Aβ) plaques have raised new hopes for the treatment of Alzheimer's disease (AD). Two particularly promising passive immunization therapies currently being investigated include ... ...

Abstract	Immunization strategies which aid in the clearance of beta-amyloid (Aβ) plaques have raised new hopes for the treatment of Alzheimer's disease (AD). Two particularly promising passive immunization therapies currently being investigated include intravenous immunoglobulins (IVIG) containing Aβ antibodies and specifically developed monoclonal antibodies for Aβ. These Aβ antibodies may reduce amyloid accumulation in the brain by binding to the amyloid peptide and drawing it in through the blood-brain barrier for subsequent removal from the capillaries. However, as this strategy aims at removing extracellular amyloid through cerebral vessels, a redistribution of amyloid pathology may manifest as increased cerebral amyloid angiopathy (CAA). CAA occurs when Aβ becomes embedded in the walls of cerebral vessels associated with weakening of the vessel walls. Antibody mediated Aβ clearance from the parenchyma could significantly increase the Aβ burden in the vessel lumen and wall, therefore increasing the risk of vessel rupture and hemorrhage. This chapter will review the current literature on Aβ immunotherapy for AD and explore the mechanisms as well as possible risks of amyloid clearance treatment, particularly cerebral amyloid angiopathy.
Language	English
Publishing date	2014-09-09
Publishing country	United States
Document type	Journal Article
ISSN	1935-2514
ISSN	1935-2514
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Article: Neuropsychiatric update: neuroimaging schizophrenia.

Kile, Shawn J

Psychopharmacology bulletin

2007 Volume 40, Issue 4, Page(s) 156–167

Abstract: Neuroimaging has revitalized the quest for the neurobiology of schizophrenia. The various neuroimaging modalities used in research are described including CT, MRI, PET, SPECT, fMRI, and DTI. Prominent and consistent neuroanatomical findings in the ... ...

Abstract	Neuroimaging has revitalized the quest for the neurobiology of schizophrenia. The various neuroimaging modalities used in research are described including CT, MRI, PET, SPECT, fMRI, and DTI. Prominent and consistent neuroanatomical findings in the neuroimaging literature of schizophrenia are outlined. These findings, including enlargement of the lateral ventricles, undersized superior temporal gyrus, and prefrontal abnormalities, are supported with neuropathological studies of schizophrenia. Additionally, these findings are correlated with the clinical symptoms of schizophrenia. Neurochemical imaging studies of schizophrenia are reviewed and noted to support dopaminergic dysregulation consistent with the dopamine hypothesis. Finally, current and near-future clinical uses of neuroimaging are described.
MeSH term(s)	Humans ; Magnetic Resonance Imaging ; Neuroimaging/methods ; Positron-Emission Tomography ; Schizophrenia/diagnosis ; Schizophrenia/drug therapy ; Tomography, Emission-Computed, Single-Photon
Language	English
Publishing date	2007
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	4113-0
ISSN	0048-5764 ; 0376-0162
ISSN	0048-5764 ; 0376-0162
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Zs.A 958: Show issues

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Article: Neurodevelopmental pathways to aggression: a model to understand and target treatment in youth.

Sugden, Steven G / Kile, Shawn J / Hendren, Robert L

The Journal of neuropsychiatry and clinical neurosciences

2006 Volume 18, Issue 3, Page(s) 302–317

Abstract: The authors describe a neurodevelopmentally relevant, clinically derived model for understanding and treating aggressive behavior in youth. Based on case experience and literature review, the authors divide aggressive behavior into five symptomatic ... ...

Abstract	The authors describe a neurodevelopmentally relevant, clinically derived model for understanding and treating aggressive behavior in youth. Based on case experience and literature review, the authors divide aggressive behavior into five symptomatic domains with respective neurobiological/neurodevelopmental underpinnings. These five symptom domains (impulsivity, affective instability, anxious/hyperarousal, cognitive disorganization, and predatory aggression) emerge as logical and clinically useful targets for treatment. The authors aim to establish a relationship between these symptom domains and brain structure and function that offers a clinically relevant approach to the complexities of understanding aggression and its treatment.
MeSH term(s)	Adolescent ; Adrenergic Agents/therapeutic use ; Aggression/physiology ; Aggression/psychology ; Anti-Anxiety Agents/therapeutic use ; Antidepressive Agents/therapeutic use ; Antipsychotic Agents/therapeutic use ; Anxiety/physiopathology ; Arousal/physiology ; Central Nervous System Stimulants/therapeutic use ; Child ; Cognition/physiology ; Female ; Humans ; Hypothalamo-Hypophyseal System/physiopathology ; Impulsive Behavior/physiopathology ; Impulsive Behavior/psychology ; Impulsive Behavior/therapy ; Male ; Mood Disorders/physiopathology ; Mood Disorders/psychology ; Mood Disorders/therapy ; Nervous System/growth & development ; Nervous System/physiopathology
Chemical Substances	Adrenergic Agents ; Anti-Anxiety Agents ; Antidepressive Agents ; Antipsychotic Agents ; Central Nervous System Stimulants
Language	English
Publishing date	2006
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	1036340-3
ISSN	1545-7222 ; 0895-0172
ISSN (online)	1545-7222
ISSN	0895-0172
DOI	10.1176/jnp.2006.18.3.302
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Zs.A 2633: Show issues

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Article: Bithalamic lesions of butane encephalopathy.

Kile, Shawn J / Camilleri, Christopher C / Latchaw, Richard E / Tharp, Barry R

Pediatric neurology

2006 Volume 35, Issue 6, Page(s) 439–441

Abstract: Butane inhalation can cause serious medical complications and is particularly toxic to the nervous system. This is a report of an acutely encephalopathic youth with prominent abulia. MRI revealed severe bithalamic injury attributed to butane toxicity. ... ...

Abstract	Butane inhalation can cause serious medical complications and is particularly toxic to the nervous system. This is a report of an acutely encephalopathic youth with prominent abulia. MRI revealed severe bithalamic injury attributed to butane toxicity. Clinical issues, including particular radiologic findings, related to butane inhalation are reviewed.
MeSH term(s)	Acute Disease ; Administration, Inhalation ; Adolescent ; Akinetic Mutism/chemically induced ; Akinetic Mutism/pathology ; Butanes/administration & dosage ; Butanes/adverse effects ; Female ; Functional Laterality ; Humans ; Magnetic Resonance Imaging ; Substance-Related Disorders/complications ; Thalamic Diseases/chemically induced ; Thalamic Diseases/pathology
Chemical Substances	Butanes ; butane (6LV4FOR43R)
Language	English
Publishing date	2006-12
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	639164-3
ISSN	1873-5150 ; 0887-8994
ISSN (online)	1873-5150
ISSN	0887-8994
DOI	10.1016/j.pediatrneurol.2006.06.018
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Zs.A 2260: Show issues

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Article ; Online: Reduction of Amyloid in the Brain and Retina After Treatment With IVIG for Mild Cognitive Impairment.

Kile, Shawn / Au, William / Parise, Carol / Sohi, Jaideep / Yarbrough, Tracy / Czeszynski, Alan / Johnson, Ken / Redline, Dan / Donnel, Tammy / Hankins, Andrea / Rose, Kimberley

American journal of Alzheimer's disease and other dementias

2020 Volume 35, Page(s) 1533317519899800

Abstract: Objective: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS).: Methods: Five subjects with MCI underwent baseline Florbetapir ... ...

Abstract	Objective: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS). Methods: Five subjects with MCI underwent baseline Florbetapir positron emission tomography and retinal autofluorescent imaging. All were administered IVIG (Octagam 10%) at 0.4 g/kg every 14 days for a total of 5 infusions. After 3 months, standard uptake value ratio (SUVR) and amyloid retinal deposits were reassessed. Results: Three subjects had a reduction in amyloid SUVR and all 5 subjects had a reduction in amyloid retinal deposits in at least 1 eye. Conclusions: A short course of IVIG over 2 months removes a measurable amount of amyloid from the CNS in persons with MCI.
MeSH term(s)	Aged ; Amyloid beta-Peptides/metabolism ; Aniline Compounds ; Brain/diagnostic imaging ; Brain/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/drug therapy ; Ethylene Glycols ; Female ; Humans ; Immunoglobulins, Intravenous/administration & dosage ; Male ; Positron-Emission Tomography ; Retina/diagnostic imaging
Chemical Substances	Amyloid beta-Peptides ; Aniline Compounds ; Ethylene Glycols ; Immunoglobulins, Intravenous ; Octagam ; florbetapir (6867Q6IKOD)
Language	English
Publishing date	2020-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283069-0
ISSN	1938-2731 ; 0895-5336 ; 1082-5207 ; 1533-3175
ISSN (online)	1938-2731
ISSN	0895-5336 ; 1082-5207 ; 1533-3175
DOI	10.1177/1533317519899800
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Zs.A 3299: Show issues

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Article ; Online: Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer's disease.

Koronyo, Yosef / Biggs, David / Barron, Ernesto / Boyer, David S / Pearlman, Joel A / Au, William J / Kile, Shawn J / Blanco, Austin / Fuchs, Dieu-Trang / Ashfaq, Adeel / Frautschy, Sally / Cole, Gregory M / Miller, Carol A / Hinton, David R / Verdooner, Steven R / Black, Keith L / Koronyo-Hamaoui, Maya

JCI insight

2017 Volume 2, Issue 16

Abstract: Background: Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal ... ...

Abstract	Background: Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits. Methods: Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients. Results: Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031). Conclusion: The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring. Funding: National Institute on Aging award (AG044897) and The Saban and The Marciano Family Foundations.
Language	English
Publishing date	2017-08-17
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.93621
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Article: Neuroleptic malignant syndrome with dermatologic complications.

Sugden, Steven G / Bourgeois, James A / Kile, Shawn J / Hilty, Donald M

Journal of clinical psychopharmacology

2004 Volume 24, Issue 6, Page(s) 676–678

MeSH term(s)	Antipsychotic Agents/adverse effects ; Drug Hypersensitivity/complications ; Drug Hypersensitivity/immunology ; Humans ; Male ; Middle Aged ; Neuroleptic Malignant Syndrome/complications ; Skin Diseases/chemically induced ; Skin Diseases/complications
Chemical Substances	Antipsychotic Agents
Language	English
Publishing date	2004-11-05
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	604631-9
ISSN	1533-712X ; 0271-0749
ISSN (online)	1533-712X
ISSN	0271-0749
DOI	10.1097/01.jcp.0000145346.61041.18
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Zs.A 1664: Show issues

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Article ; Online: Alzheimer abnormalities of the amygdala with Klüver-Bucy syndrome symptoms: an amygdaloid variant of Alzheimer disease.

Kile, Shawn J / Ellis, William G / Olichney, John M / Farias, Sarah / DeCarli, Charles

Archives of neurology

2008 Volume 66, Issue 1, Page(s) 125–129

Abstract: Background: Neurofibrillary tangles and beta-amyloid plaques have been observed in the amygdala in Alzheimer disease. A disproportionate abundance of this abnormality in the amygdala may cause behavioral symptoms similar to Klüver-Bucy syndrome.: ... ...

Abstract	Background: Neurofibrillary tangles and beta-amyloid plaques have been observed in the amygdala in Alzheimer disease. A disproportionate abundance of this abnormality in the amygdala may cause behavioral symptoms similar to Klüver-Bucy syndrome. Objectives: To describe an atypical behavioral presentation of Alzheimer disease and to review the literature on the subject. Design: Case study. Setting: Outpatient specialty clinic. Patient: A 70-year-old man with progressive behavioral symptoms of hyperorality, hypersexuality, hypermetamorphosis, visual agnosia, hyperphagia, and apathy who died at age 77 of asphyxiation on a foreign object. Main outcome measures: Clinical symptomatology, brain imaging, and neuropathology. Results: The pathologic diagnosis was Alzheimer disease with abundant tangles and plaques in the lateral amygdala. Conclusions: This case represents a variant of Alzheimer disease with prominent amygdala abnormalities and a Klüver-Bucy phenotype that was misdiagnosed as frontotemporal dementia. Clinical and imaging findings that may aid in accurate diagnosis are reviewed.
MeSH term(s)	Aged ; Alzheimer Disease/complications ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Amygdala/diagnostic imaging ; Amygdala/pathology ; Amygdala/physiopathology ; Autopsy ; Dementia/diagnosis ; Diagnosis, Differential ; Diagnostic Errors/prevention & control ; Disease Progression ; Fatal Outcome ; Humans ; Kluver-Bucy Syndrome/etiology ; Kluver-Bucy Syndrome/pathology ; Kluver-Bucy Syndrome/physiopathology ; Magnetic Resonance Imaging ; Male ; Neurofibrillary Tangles/pathology ; Neuropsychological Tests ; Plaque, Amyloid/pathology ; Positron-Emission Tomography ; Retrospective Studies
Language	English
Publishing date	2008-12-30
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80049-1
ISSN	1538-3687 ; 0003-9942
ISSN (online)	1538-3687
ISSN	0003-9942
DOI	10.1001/archneurol.2008.517
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Article: Brain regions showing increased activation by threat-related words in panic disorder.

Maddock, Richard J / Buonocore, Michael H / Kile, Shawn J / Garrett, Amy S

Neuroreport

2003 Volume 14, Issue 3, Page(s) 325–328

Abstract: Threat-related stimuli consistently activate the posterior cingulate cortex in normal subjects and have exaggerated effects on memory in patients with panic disorder. We hypothesized that panic patients would show increased response to threat-related ... ...

Abstract	Threat-related stimuli consistently activate the posterior cingulate cortex in normal subjects and have exaggerated effects on memory in patients with panic disorder. We hypothesized that panic patients would show increased response to threat-related stimuli in the posterior cingulate cortex. While undergoing fMRI, six panic patients and eight healthy volunteers made valence judgements of threat-related and neutral words. Both groups showed threat-related activation in the left posterior cingulate and left middle frontal cortices, but the activation was significantly greater in panic patients. Panic patients also had more right>left asymmetry of activation in the mid-parahippocampal region. The increased responsivity observed in the posterior cingulate and dorsolateral prefrontal cortices is consistent with the hypothesis that panic disorder patients engage in more extensive memory processing of threat-related stimuli.
MeSH term(s)	Adult ; Aggression ; Brain/physiopathology ; Brain Mapping ; Fear/physiology ; Female ; Frontal Lobe/physiopathology ; Gyrus Cinguli/physiopathology ; Humans ; Language ; Magnetic Resonance Imaging ; Male ; Panic Disorder/physiopathology ; Parahippocampal Gyrus/physiopathology ; Prefrontal Cortex/physiopathology ; Reference Values
Language	English
Publishing date	2003-03-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/00001756-200303030-00006
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Zs.A 3118: Show issues

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Article: Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla.

Maddock, Richard J / Buonocore, Michael H / Lavoie, Shawn P / Copeland, Linda E / Kile, Shawn J / Richards, Anne L / Ryan, John M

Psychiatry research

2006 Volume 148, Issue 1, Page(s) 47–54

Abstract: Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses ... ...

Abstract	Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using (1)H-MRS at 1.5 Tesla with a long echo time (TE=288 ms), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 T and show that variations in blood glucose across the normal range have little effect on this response.
MeSH term(s)	Adult ; Aspartic Acid/analogs & derivatives ; Aspartic Acid/metabolism ; Blood Glucose/metabolism ; Brain/physiopathology ; Choline/metabolism ; Creatine/metabolism ; Energy Metabolism/physiology ; Fasting/physiology ; Female ; Humans ; Hyperglycemia/physiopathology ; Lactic Acid/metabolism ; Magnetic Resonance Spectroscopy ; Male ; Neurons/physiology ; Pattern Recognition, Visual/physiology ; Photic Stimulation ; Reference Values ; Signal Processing, Computer-Assisted ; Visual Cortex/physiology
Chemical Substances	Blood Glucose ; Aspartic Acid (30KYC7MIAI) ; Lactic Acid (33X04XA5AT) ; N-acetylaspartate (997-55-7) ; Creatine (MU72812GK0) ; Choline (N91BDP6H0X)
Language	English
Publishing date	2006-11-22
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	445361-x
ISSN	1872-7123 ; 1872-7506 ; 0165-1781 ; 0925-4927
ISSN (online)	1872-7123 ; 1872-7506
ISSN	0165-1781 ; 0925-4927
DOI	10.1016/j.pscychresns.2006.02.004
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