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Article: Screening and Targeting Risk Factors for Prodromal Synucleinopathy: Taking Steps toward a Prescriptive Multi-modal Framework.

Neilson, Lee E / Quinn, Joseph F / Lim, Miranda M

2023 Volume 14, Issue 4, Page(s) 1243–1263

Abstract: As the prevalence of Parkinson's disease (PD) grows, so too does the population at-risk of developing PD, those in the so-called prodromal period. This period can span from those experiencing subtle motor deficits yet not meeting full diagnostic criteria ...

Abstract	As the prevalence of Parkinson's disease (PD) grows, so too does the population at-risk of developing PD, those in the so-called prodromal period. This period can span from those experiencing subtle motor deficits yet not meeting full diagnostic criteria or those with physiologic markers of disease alone. Several disease-modifying therapies have failed to show a neuroprotective effect. A common criticism is that neurodegeneration, even in the early motor stages, has advanced too far for neuro-restoration-based interventions to be effective. Therefore, identifying this early population is essential. Once identified, these patients could then potentially benefit from sweeping lifestyle modifications to alter their disease trajectory. Herein, we review the literature on risk factors for, and prodromal symptoms of, PD with an emphasis on ones which may be modifiable in the earliest possible stages. We propose a process for identifying this population and speculate on some strategies which may modulate disease trajectory. Ultimately, this proposal warrants prospective studies.
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2625789-0
ISSN	2152-5250
ISSN	2152-5250
DOI	10.14336/AD.2022.1024
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Lost in Translation? Finding Our Way To Effective Alzheimer's Disease Therapies.

Quinn, Joseph F

Journal of Alzheimer's disease : JAD

2018 Volume 64, Issue s1, Page(s) S33–S39

Abstract: Efforts over the past two decades to develop effective disease-modifying treatments for Alzheimer's disease have been disappointing, while parallel efforts in another chronic neurologic disease, multiple sclerosis, have been remarkably productive. In an ... ...

Abstract	Efforts over the past two decades to develop effective disease-modifying treatments for Alzheimer's disease have been disappointing, while parallel efforts in another chronic neurologic disease, multiple sclerosis, have been remarkably productive. In an effort to advance development of therapeutics for Alzheimer's disease, these two fields are contrasted in terms of the utility of animal models, definition of study populations, and utility of biomarkers. Possible solutions are suggested, and the review concludes with description of some active peer-reviewed, publicly funded clinical studies which address some of the identified weaknesses in past clinical trials for age-related dementia.
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/therapy ; Animals ; Biomarkers/metabolism ; Clinical Trials as Topic/methods ; Disease Models, Animal ; Humans ; Translational Medical Research/methods
Chemical Substances	Biomarkers
Language	English
Publishing date	2018-06-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-179930
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Article ; Online: Do ω-3 Fatty Acids Regulate Cerebral β Amyloid?

Quinn, Joseph F

JAMA neurology

2016 Volume 73, Issue 10, Page(s) 1183–1184

MeSH term(s)	Alzheimer Disease ; Amyloid beta-Peptides ; Fatty Acids, Omega-3 ; Humans
Chemical Substances	Amyloid beta-Peptides ; Fatty Acids, Omega-3
Language	English
Publishing date	2016-08-15
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2702023-X
ISSN	2168-6157 ; 2168-6149
ISSN (online)	2168-6157
ISSN	2168-6149
DOI	10.1001/jamaneurol.2016.2534
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Article ; Online: Analysis of the longitudinal stability of human plasma miRNAs and implications for disease biomarkers.

Sandau, Ursula S / Wiedrick, Jack T / McFarland, Trevor J / Galasko, Douglas R / Fanning, Zoe / Quinn, Joseph F / Saugstad, Julie A

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2148

Abstract: There is great interest in developing clinical biomarker assays that can aid in non-invasive diagnosis and/or monitoring of human diseases, such as cancer, cardiovascular disease, and neurological diseases. Yet little is known about the longitudinal ... ...

Abstract	There is great interest in developing clinical biomarker assays that can aid in non-invasive diagnosis and/or monitoring of human diseases, such as cancer, cardiovascular disease, and neurological diseases. Yet little is known about the longitudinal stability of miRNAs in human plasma. Here we assessed the intraindividual longitudinal stability of miRNAs in plasma from healthy human adults, and the impact of common factors (e.g., hemolysis, age) that may confound miRNA data. We collected blood by venipuncture biweekly over a 3-month period from 22 research participants who had fasted overnight, isolated total RNA, then performed miRNA qPCR. Filtering and normalization of the qPCR data revealed amplification of 134 miRNAs, 74 of which had high test-retest reliability and low percentage level drift, meaning they were stable in an individual over the 3-month time period. We also determined that, of nuisance factors, hemolysis and tobacco use have the greatest impact on miRNA levels and variance. These findings support that many miRNAs show intraindividual longitudinal stability in plasma from healthy human adults, including some reported as candidate biomarkers for Alzheimer's disease.
MeSH term(s)	Adult ; Humans ; MicroRNAs/genetics ; Hemolysis ; Reproducibility of Results ; Plasma ; Biomarkers
Chemical Substances	MicroRNAs ; Biomarkers
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52681-5
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Article ; Online: Lifelong Association of Disorders Related to Military Trauma with Subsequent Parkinson's Disease.

Scott, Gregory D / Neilson, Lee E / Woltjer, Randy / Quinn, Joseph F / Lim, Miranda M

Movement disorders : official journal of the Movement Disorder Society

2023 Volume 38, Issue 8, Page(s) 1483–1492

Abstract: Background: Trauma-related disorders such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are emerging as risk factors for Parkinson's disease (PD), but their association with development of PD and independence from comorbid ... ...

Abstract	Background: Trauma-related disorders such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are emerging as risk factors for Parkinson's disease (PD), but their association with development of PD and independence from comorbid disorders remains unknown. Objective: To examine TBI and PTSD related to early trauma in military veterans using a case-control study. Methods: PD was identified by International Classification of Diseases (ICD) code, recurrent PD-specific prescriptions, and availability of 5+ years of earlier records. Validation was performed by chart review by a movement disorder-trained neurologist. Control subjects were matched 4:1 by age, duration of preceding health care, race, ethnicity, birth year, and sex. TBI and PTSD were identified by ICD code and onset based on active duty. Association and interaction were measured for TBI and PTSD with PD going back 60 years. Interaction was measured for comorbid disorders. Results: A total of 71,933 cases and 287,732 controls were identified. TBI and PTSD increased odds of subsequent PD at all preceding 5-year intervals back to year -60 (odds ratio range: 1.5 [1.4, 1.7] to 2.1 [2.0, 2.1]). TBI and PTSD showed synergism (synergy index range: 1.14 [1.09, 1.29] to 1.28 [1.09, 1.51]) and additive association (odds ratio range: 2.2 [1.6, 2.8] to 2.7 [2.5, 2.8]). Chronic pain and migraine showed greatest synergy with PTSD and TBI. Effect sizes for trauma-related disorders were comparable with established prodromal disorders. Conclusions: TBI and PTSD are associated with later PD and are synergistic with chronic pain and migraine. These findings provide evidence for TBI and PTSD as risk factors preceding PD by decades and could aid in prognostic calculation and earlier intervention. © 2023 International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
MeSH term(s)	Humans ; Parkinson Disease/complications ; Parkinson Disease/epidemiology ; Veterans ; Case-Control Studies ; Comorbidity ; Chronic Pain ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/epidemiology ; Stress Disorders, Post-Traumatic/complications ; Stress Disorders, Post-Traumatic/epidemiology ; Migraine Disorders
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29457
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Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 238: Show issues

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Article: Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease.

Neilson, Lee E / Quinn, Joseph F / Gray, Nora E

Antioxidants (Basel, Switzerland)

2020 Volume 10, Issue 1

Abstract: Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated ... ...

Abstract	Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation.
Language	English
Publishing date	2020-12-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10010028
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Book: Dementia

Quinn, Joseph F

(Neurology in practice)

2014

Author's details	edited by Joseph F. Quinn
Series title	Neurology in practice
MeSH term(s)	Dementia
Language	English
Size	xi, 176 pages :, illustrations
Document type	Book
ISBN	9780470674246 ; 0470674245
Database	Catalogue of the US National Library of Medicine (NLM)

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Article ; Online: Biomarkers for Alzheimer's disease: showing the way or leading us astray?

Quinn, Joseph F

Journal of Alzheimer's disease : JAD

2012 Volume 33 Suppl 1, Page(s) S371–6

Abstract: The indolent nature of Alzheimer's disease, coupled with burgeoning interest in a "presymptomatic" stage of disease, has motivated efforts to identify, validate, and exploit surrogate disease markers for trials of disease-modifying or preventive ... ...

Abstract	The indolent nature of Alzheimer's disease, coupled with burgeoning interest in a "presymptomatic" stage of disease, has motivated efforts to identify, validate, and exploit surrogate disease markers for trials of disease-modifying or preventive strategies. Many of these efforts have been productive, and biomarkers are now routinely applied in selection of study subjects and evaluation of outcomes in clinical trials. On the other hand, biomarkers also have the capacity to lead to bad therapeutic outcomes when they determine "go- no go" decisions in early drug development. This paper reviews several reports of biomarker studies which illustrate the great potential, for both good and ill, of biomarkers of Alzheimer's disease.
MeSH term(s)	Alzheimer Disease/diagnosis ; Alzheimer Disease/metabolism ; Biomarkers/metabolism ; Humans
Chemical Substances	Biomarkers
Language	English
Publishing date	2012-07-06
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-2012-129022
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Article ; Online: Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of

Alcázar Magaña, Armando / Vaswani, Ashish / Brown, Kevin S / Jiang, Yuan / Alam, Md Nure / Caruso, Maya / Lak, Parnian / Cheong, Paul / Gray, Nora E / Quinn, Joseph F / Soumyanath, Amala / Stevens, Jan F / Maier, Claudia S

Molecules (Basel, Switzerland)

2024 Volume 29, Issue 4

Abstract: Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, ... ...

Abstract	Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of
MeSH term(s)	Humans ; Amyloid beta-Peptides/toxicity ; Alzheimer Disease/drug therapy ; Plant Extracts/pharmacology ; Cognition ; Centella/chemistry ; Triterpenes/analysis ; Biological Assay ; Computer Simulation ; Quinic Acid/analogs & derivatives
Chemical Substances	Amyloid beta-Peptides ; Plant Extracts ; Triterpenes ; caffeoylquinic acid ; Quinic Acid (058C04BGYI)
Language	English
Publishing date	2024-02-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules29040838
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Article: Mode of administration influences plasma levels of active

Speers, Alex B / Wright, Kirsten M / Brandes, Mikah S / Kedjejian, Nareg / Matthews, Donald G / Caruso, Maya / Harris, Christopher J / Koike, Seiji / Nguyen, Thuan / Quinn, Joseph F / Soumyanath, Amala / Gray, Nora E

Frontiers in neuroscience

2024 Volume 18, Page(s) 1277626

Abstract: Introduction: A water extract of : Methods: Eight-to-nine-month-old male and female 5xFAD mice and their wild-type littermates were administered CAW in their diet or drinking water (0 or 1,000 mg/kg/day) for five weeks. Immunohistochemistry was ... ...

Abstract	Introduction: A water extract of Methods: Eight-to-nine-month-old male and female 5xFAD mice and their wild-type littermates were administered CAW in their diet or drinking water (0 or 1,000 mg/kg/day) for five weeks. Immunohistochemistry was performed for β-amyloid (Aβ), glial fibrillary acidic protein (GFAP), and Results: CAW decreased cortical Aβ plaque burden in female 5xFAD mice administered CAW in the drinking water but had no effect on Aβ plaques in other treatment groups. CAW did not impact elevated levels of GFAP or GSL I in 5xFAD mice, regardless of sex, brain region, or mode of CAW administration. In the deep grey matter, CAW increased C3AR1 expression in 5xFAD females administered CAW in the drinking water and decreased IL-1β expression in 5xFAD males administered CAW in the diet. CAW had no effect, however, on gene expression levels of any other inflammatory mediator in the deep grey, for either sex or mode of CAW administration. Mice administered CAW in the drinking water versus the diet had significantly higher plasma levels of CAW compounds. Discussion: CAW had little impact on the neuroinflammatory markers selected for evaluation in the present study, suggesting that the cognitive benefits of CAW may not be mediated by an anti-inflammatory effect or that additional molecular markers are needed to fully characterize the effect of CAW on neuroinflammation.
Language	English
Publishing date	2024-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2024.1277626
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