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Article ; Online: Progress with Treatments for Alzheimer's Disease.

Levey, Allan I

2021 Volume 384, Issue 18, Page(s) 1762–1763

MeSH term(s)	Alzheimer Disease/drug therapy ; Amyloid beta-Peptides ; Antibodies, Monoclonal ; Brain ; Humans
Chemical Substances	Amyloid beta-Peptides ; Antibodies, Monoclonal
Language	English
Publishing date	2021-05-05
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe2103722
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Ua VI Zs.34: Show issues

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Article ; Online: Immunotherapies for Alzheimer's disease.

Golde, Todd E / Levey, Allan I

Science (New York, N.Y.)

2023 Volume 382, Issue 6676, Page(s) 1242–1244

Abstract: Antibodies targeting amyloid-β aggregates slow decline in Alzheimer's disease. ...

Abstract	Antibodies targeting amyloid-β aggregates slow decline in Alzheimer's disease.
MeSH term(s)	Humans ; Alzheimer Disease/therapy ; Amyloid beta-Peptides/immunology ; Immunotherapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Clinical Trials as Topic
Chemical Substances	Amyloid beta-Peptides ; aducanumab (105J35OE21) ; lecanemab (12PYH0FTU9) ; donanemab ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2023-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adj9255
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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Article ; Online: Alzheimer's disease: A clinical perspective and future nonhuman primate research opportunities.

Haque, Rafi U / Levey, Allan I

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 52, Page(s) 26224–26229

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the sixth leading cause of death and the most common cause of dementia worldwide. Over the last few decades, significant advancements have been made in our understanding of AD ... ...

Abstract	Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the sixth leading cause of death and the most common cause of dementia worldwide. Over the last few decades, significant advancements have been made in our understanding of AD by investigating the molecular mechanisms underlying amyloid-β and tau pathology. Despite this progress, no disease-modifying treatments exist for AD, an issue that will exacerbated by the rising costs and prevalence of the disorder. Moreover, effective therapies to address the devastating cognitive and behavioral symptoms are also urgently needed. This perspective focuses on the value of nonhuman primate (NHP) models in bridging the molecular, circuit, and behavioral levels of analysis to better understand the complex genetic and environmental/lifestyle factors that contribute to AD pathogenesis. These investigations could provide an opportunity for translating our understanding of the pathogenesis and physiological mechanisms underlying AD and related disorders into new diagnostic approaches and disease-modifying therapies to prevent disease or restore brain function for symptomatic individuals.
Language	English
Publishing date	2019-12-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1912954116
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Zs.A 1148: Show issues

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Article ; Online: Indoor Group Identification and Localization Using Privacy-Preserving Edge Computing Distributed Camera Network.

Hegde, Chaitra / Kiarashi, Yashar / Rodriguez, Amy D / Levey, Allan I / Doiron, Matthew / Kwon, Hyeokhyen / Clifford, Gari D

IEEE journal of indoor and seamless positioning and navigation

2024 Volume 2, Page(s) 51–60

Abstract: Social interaction behaviors change as a result of both physical and psychiatric problems, and it is important to identify subtle changes in group activity engagements for monitoring the mental health of patients in clinics. This work proposes a system ... ...

Abstract	Social interaction behaviors change as a result of both physical and psychiatric problems, and it is important to identify subtle changes in group activity engagements for monitoring the mental health of patients in clinics. This work proposes a system to identify when and where group formations occur in an approximately 1700 m
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ISSN	2832-7322
ISSN (online)	2832-7322
DOI	10.1109/jispin.2024.3354248
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Article ; Online: Association between Fine Particulate Matter Exposure and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease among a Cognitively Healthy Population-Based Cohort.

Casey, Emma / Li, Zhenjiang / Liang, Donghai / Ebelt, Stefanie / Levey, Allan I / Lah, James J / Wingo, Thomas S / Hüls, Anke

Environmental health perspectives

2024 Volume 132, Issue 4, Page(s) 47001

Abstract: Background: Epidemiological evidence suggests air pollution adversely affects cognition and increases the risk of Alzheimer's disease (AD), but little is known about the biological effects of fine particulate matter (: Objectives: We investigated the ...

Abstract	Background: Epidemiological evidence suggests air pollution adversely affects cognition and increases the risk of Alzheimer's disease (AD), but little is known about the biological effects of fine particulate matter ( Objectives: We investigated the association between 1-, 3-, and 5-y exposure to ambient and traffic-related Methods: We conducted a cross-sectional analysis using data from 1,113 cognitively healthy adults (45-75 y of age) from the Emory Healthy Brain Study in Georgia in the United States. CSF biomarker concentrations of Results: Interquartile range (IQR; Conclusion: In our study, consistent trends were found between 1-y
MeSH term(s)	Adult ; Humans ; United States ; Particulate Matter/analysis ; Air Pollutants/analysis ; Alzheimer Disease/epidemiology ; Cross-Sectional Studies ; Environmental Exposure/analysis ; Air Pollution/analysis ; Biomarkers/analysis
Chemical Substances	Particulate Matter ; Air Pollutants ; Biomarkers
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/EHP13503
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Zs.B 1360: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 379: Show issues

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Article ; Online: Disentangling Visual Exploration Differences in Cognitive Impairment.

Jiang, Zifan / Seyedi, Salman / Vickers, Kayci L / Manzanares, Cecelia M / Lah, James J / Levey, Allan I / Clifford, Gari D

IEEE transactions on bio-medical engineering

2024 Volume 71, Issue 4, Page(s) 1197–1208

Abstract: Objective: Individuals with cognitive impairment (CI) exhibit different oculomotor functions and viewing behaviors. In this work we aimed to quantify the differences in these functions with CI severity, and assess general CI and specific cognitive ... ...

Abstract	Objective: Individuals with cognitive impairment (CI) exhibit different oculomotor functions and viewing behaviors. In this work we aimed to quantify the differences in these functions with CI severity, and assess general CI and specific cognitive functions related to visual exploration behaviors. Methods: A validated passive viewing memory test with eyetracking was administered to 348 healthy controls and CI individuals. Spatiotemporal properties of the scanpath, the semantic category of the viewed regions, and other composite features were extracted from the estimated eyegaze locations on the corresponding pictures displayed during the test. These features were then used to characterize viewing patterns, classify cognitive impairment, and estimate scores in various neuropsychological tests using machine learning. Results: Statistically significant differences in spatial, spatiotemporal, and semantic features were found between healthy controls and individuals with CI. The CI group spent more time gazing at the center of the image, looked at more regions of interest (ROI), transitioned less often between ROI yet in a more unpredictable manner, and exhibited different semantic preferences. A combination of these features achieved an area under the receiver-operator curve of 0.78 in differentiating CI individuals from controls. Statistically significant correlations were identified between actual and estimated CI scores and other neuropsychological tests. Conclusion: Evaluating visual exploration behaviors provided quantitative and systematic evidence of differences in CI individuals, leading to an improved approach for passive cognitive impairment screening. Significance: The proposed passive, accessible, and scalable approach could help with earlier detection and a better understanding of cognitive impairment.
MeSH term(s)	Humans ; Cognitive Dysfunction/diagnosis ; Neuropsychological Tests ; Cognition ; Machine Learning
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	160429-6
ISSN	1558-2531 ; 0018-9294
ISSN (online)	1558-2531
ISSN	0018-9294
DOI	10.1109/TBME.2023.3330976
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Zs.A 425: Show issues

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Article ; Online: Brain cholesterol and Alzheimer's disease: challenges and opportunities in probe and drug development.

Ahmed, Hazem / Wang, Yuqin / Griffiths, William J / Levey, Allan I / Pikuleva, Irina / Liang, Steven H / Haider, Ahmed

Brain : a journal of neurology

2024 Volume 147, Issue 5, Page(s) 1622–1635

Abstract: Cholesterol homeostasis is impaired in Alzheimer's disease; however, attempts to modulate brain cholesterol biology have not translated into tangible clinical benefits for patients to date. Several recent milestone developments have substantially ... ...

Abstract	Cholesterol homeostasis is impaired in Alzheimer's disease; however, attempts to modulate brain cholesterol biology have not translated into tangible clinical benefits for patients to date. Several recent milestone developments have substantially improved our understanding of how excess neuronal cholesterol contributes to the pathophysiology of Alzheimer's disease. Indeed, neuronal cholesterol was linked to the formation of amyloid-β and neurofibrillary tangles through molecular pathways that were recently delineated in mechanistic studies. Furthermore, remarkable advances in translational molecular imaging have now made it possible to probe cholesterol metabolism in the living human brain with PET, which is an important prerequisite for future clinical trials that target the brain cholesterol machinery in Alzheimer's disease patients-with the ultimate aim being to develop disease-modifying treatments. This work summarizes current concepts of how the biosynthesis, transport and clearance of brain cholesterol are affected in Alzheimer's disease. Further, current strategies to reverse these alterations by pharmacotherapy are critically discussed in the wake of emerging translational research tools that support the assessment of brain cholesterol biology not only in animal models but also in patients with Alzheimer's disease.
Language	English
Publishing date	2024-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awae028
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Ui II Zs.26: Show issues

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Article ; Online: Machine Learning Selection of Most Predictive Brain Proteins Suggests Role of Sugar Metabolism in Alzheimer's Disease.

Tandon, Raghav / Levey, Allan I / Lah, James J / Seyfried, Nicholas T / Mitchell, Cassie S

Journal of Alzheimer's disease : JAD

2023 Volume 92, Issue 2, Page(s) 411–424

Abstract: Background: The complex and not yet fully understood etiology of Alzheimer's disease (AD) shows important proteopathic signs which are unlikely to be linked to a single protein. However, protein subsets from deep proteomic datasets can be useful in ... ...

Abstract	Background: The complex and not yet fully understood etiology of Alzheimer's disease (AD) shows important proteopathic signs which are unlikely to be linked to a single protein. However, protein subsets from deep proteomic datasets can be useful in stratifying patient risk, identifying stage dependent disease markers, and suggesting possible disease mechanisms. Objective: The objective was to identify protein subsets that best classify subjects into control, asymptomatic Alzheimer's disease (AsymAD), and AD. Methods: Data comprised 6 cohorts; 620 subjects; 3,334 proteins. Brain tissue-derived predictive protein subsets for classifying AD, AsymAD, or control were identified and validated with label-free quantification and machine learning. Results: A 29-protein subset accurately classified AD (AUC = 0.94). However, an 88-protein subset best predicted AsymAD (AUC = 0.92) or Control (AUC = 0.92) from AD (AUC = 0.98). AD versus Control: APP, DHX15, NRXN1, PBXIP1, RABEP1, STOM, and VGF. AD versus AsymAD: ALDH1A1, BDH2, C4A, FABP7, GABBR2, GNAI3, PBXIP1, and PRKAR1B. AsymAD versus Control: APP, C4A, DMXL1, EXOC2, PITPNB, RABEP1, and VGF. Additional predictors: DNAJA3, PTBP2, SLC30A9, VAT1L, CROCC, PNP, SNCB, ENPP6, HAPLN2, PSMD4, and CMAS. Conclusion: Biomarkers were dynamically separable across disease stages. Predictive proteins were significantly enriched to sugar metabolism.
MeSH term(s)	Humans ; Alzheimer Disease/metabolism ; Proteomics ; Brain/metabolism ; Machine Learning ; Sugars/metabolism ; HSP40 Heat-Shock Proteins/metabolism ; Hydroxybutyrate Dehydrogenase/metabolism ; Proteins/metabolism
Chemical Substances	Sugars ; DNAJA3 protein, human ; HSP40 Heat-Shock Proteins ; BDH2 protein, human (EC 1.1.1.30) ; Hydroxybutyrate Dehydrogenase (EC 1.1.1.30) ; DMXL1 protein, human ; Proteins
Language	English
Publishing date	2023-04-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-220683
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Article: Disentangling visual exploration differences in cognitive impairment.

Jiang, Zifan / Seyedi, Salman / Vickers, Kayci L / Manzanares, Cecelia M / Lah, James J / Levey, Allan I / Clifford, Gari D

medRxiv : the preprint server for health sciences

2023

Abstract: Objective: Compared to individuals without cognitive impairment (CI), those with CI exhibit differences in both basic oculomotor functions and complex viewing behaviors. However, the characteristics of the differences and how those differences relate to ...

Abstract	Objective: Compared to individuals without cognitive impairment (CI), those with CI exhibit differences in both basic oculomotor functions and complex viewing behaviors. However, the characteristics of the differences and how those differences relate to various cognitive functions have not been widely explored. In this work we aimed to quantify those differences and assess general cognitive impairment and specific cognitive functions. Methods: A validated passive viewing memory test with eyetracking was administered to 348 healthy controls and CI individuals. Spatial, temporal, semantic, and other composite features were extracted from the estimated eye-gaze locations on the corresponding pictures displayed during the test. These features were then used to characterize viewing patterns, classify cognitive impairment, and estimate scores in various neuropsychological tests using machine learning. Results: Statistically significant differences in spatial, spatiotemporal, and semantic features were found between healthy controls and individuals with CI. CI group spent more time gazing at the center of the image, looked at more regions of interest (ROI), transitioned less often between ROI yet in a more unpredictable manner, and had different semantic preferences. A combination of these features achieved an area under the receiver-operator curve of 0.78 in differentiating CI individuals from controls. Statistically significant correlations were identified between actual and estimated MoCA scores and other neuropsychological tests. Conclusion: Evaluating visual exploration behaviors provided quantitative and systematic evidence of differences in CI individuals, leading to an improved approach for passive cognitive impairment screening. Significance: The proposed passive, accessible, and scalable approach could help with earlier detection and a better understanding of cognitive impairment.
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.17.23290054
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Article: Promoting Healthy Aging: Public Health as a Leader for Reducing Dementia Risk.

Jackson, Eva M J / O'Brien, Kelly / McGuire, Lisa C / Baumgart, Matthew / Gore, Janelle / Brandt, Katie / Levey, Allan I / Lamont, Helen

The Public policy and aging report

2023 Volume 33, Issue 2, Page(s) 92–95

Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2740987-9
ISSN	2053-4892 ; 1055-3037
ISSN (online)	2053-4892
ISSN	1055-3037
DOI	10.1093/ppar/prad011
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