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Article ; Online: The neuroimmune axis of Alzheimer’s disease

Mehdi Jorfi / Anna Maaser-Hecker / Rudolph E. Tanzi

Genome Medicine, Vol 15, Iss 1, Pp 1-

2023 Volume 25

Abstract: Abstract Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder ...

Abstract	Abstract Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial and pathological roles for innate immune genes and immune cells, including peripheral immune cells such as T cells, which can infiltrate the brain and either ameliorate or exacerbate AD neuropathogenesis. These findings support a neuroimmune axis of AD, in which the interplay of adaptive and innate immune systems inside and outside the brain critically impacts the etiology and pathogenesis of AD. In this review, we discuss the complexities of AD neuropathology at the levels of genetics and cellular physiology, highlighting immune signaling pathways and genes associated with AD risk and interactions among both innate and adaptive immune cells in the AD brain. We emphasize the role of peripheral immune cells in AD and the mechanisms by which immune cells, such as T cells and monocytes, influence AD neuropathology, including microglial clearance of amyloid-β peptide, the key component of β-amyloid plaque cores, pro-inflammatory and cytotoxic activity of microglia, astrogliosis, and their interactions with the brain vasculature. Finally, we review the challenges and outlook for establishing immune-based therapies for treating and preventing AD.
Keywords	Alzheimer’s disease ; Heterogeneity ; Immune system ; β-amyloid ; Neuroimmune ; Medicine ; R ; Genetics ; QH426-470
Subject code	570
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Metabolomic Signatures of Alzheimer’s Disease Indicate Brain Region-Specific Neurodegenerative Progression

Mirela Ambeskovic / Giselle Hopkins / Tanzi Hoover / Jeffrey T. Joseph / Tony Montina / Gerlinde A. S. Metz

International Journal of Molecular Sciences, Vol 24, Iss 14769, p

2023 Volume 14769

Abstract: Pathological mechanisms contributing to Alzheimer’s disease (AD) are still elusive. Here ...

Abstract	Pathological mechanisms contributing to Alzheimer’s disease (AD) are still elusive. Here, we identified the metabolic signatures of AD in human post-mortem brains. Using 1 H NMR spectroscopy and an untargeted metabolomics approach, we identified (1) metabolomic profiles of AD and age-matched healthy subjects in post-mortem brain tissue, and (2) region-common and region-unique metabolome alterations and biochemical pathways across eight brain regions revealed that BA9 was the most affected. Phenylalanine and phosphorylcholine were mainly downregulated, suggesting altered neurotransmitter synthesis. N-acetylaspartate and GABA were upregulated in most regions, suggesting higher inhibitory activity in neural circuits. Other region-common metabolic pathways indicated impaired mitochondrial function and energy metabolism, while region-unique pathways indicated oxidative stress and altered immune responses. Importantly, AD caused metabolic changes in brain regions with less well-documented pathological alterations that suggest degenerative progression. The findings provide a new understanding of the biochemical mechanisms of AD and guide biomarker discovery for personalized risk prediction and diagnosis.
Keywords	proton nuclear magnetic resonance ( 1 H NMR) spectroscopy ; aging ; neuropathology ; neurodegenerative disease ; cognitive function ; phenylalanine ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bioluminescence Imaging with Functional Amyloid Reservoirs in Alzheimer’s Disease Models

Yang, Jing / Ding, Weihua / Zhu, Biyue / Zhen, Sherri / Kuang, Shi / Yang, Jun / Zhang, Can / Wang, Peng / Yang, Fan / Yang, Liuyue / Yin, Wei / Tanzi, Rudolph E. / Shen, Shiqian / Ran, Chongzhao

Analytical Chemistry. 2023 Sept. 15, v. 95, no. 38 p.14261-14270

2023

Abstract: ... on Alzheimer’s disease (AD). In this Article, we demonstrated that bioluminescence imaging could be used to report ...

Abstract	Bioluminescence imaging has changed the daily practice of preclinical research on cancer and other diseases over the last few decades; however, it has rarely been applied in preclinical research on Alzheimer’s disease (AD). In this Article, we demonstrated that bioluminescence imaging could be used to report the levels of amyloid beta (Aβ) species in vivo. We hypothesized that AkaLumine, a newly discovered substrate for luciferase, could bind to Aβ aggregates and plaques. We further speculated that the Aβ aggregates/fibrils/plaques could be considered as “functional amyloids”, which have a reservoir function to sequester and release AkaLumine to control the bioluminescence intensity, which could be used to report the levels of Aβs. Our hypotheses have been validated via in vitro solution tests, mimic studies with brain tissues and mice, two-photon imaging with AD mice, and in vivo bioluminescence imaging using transgenic AD mice that were virally transduced with AkaLuciferase (AkaLuc), a new luciferase that generates bioluminescence in the near-infrared window. As expected, compared to the control group, we observed that the Aβ group showed lower bioluminescence intensity due to AkaLumine sequestering at early time points, while higher intensity was due to AkaLumine releasing at later time points. Lastly, we demonstrated that this method could be used to monitor AD progression and the therapeutic effectiveness of avagacestat, a well-studied gamma-secretase inhibitor. Importantly, a good correlation (R ² = 0.81) was established between in vivo bioluminescence signals and Aβ burdens of the tested AD mice. We believe that our approach can be easily implemented into daily imaging experiments and has tremendous potential to change the daily practice of preclinical AD research.
Keywords	amyloid ; analytical chemistry ; bioluminescence ; brain ; genetically modified organisms ; luciferase ; therapeutics
Language	English
Dates of publication	2023-0915
Size	p. 14261-14270.
Publishing place	American Chemical Society
Document type	Article ; Online
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.3c02358
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells.

Verta, Roberta / Grange, Cristina / Skovronova, Renata / Tanzi, Adele / Peruzzi, Licia / Deregibus, Maria Chiara / Camussi, Giovanni / Bussolati, Benedetta

Cells

2022 Volume 11, Issue 1

Abstract: ... uptake. In order to generate EVs expressing the SARS-CoV-2 spike protein on their surface (S-EVs ... transfection with a vector coding for the S1 and S2 subunits. S-EVs were characterized using nanoparticle ... bronchial epithelial cells for assessing the internalization of labeled S-EVs using a cytofluorimetric ...

Abstract	Extracellular vesicles (EVs) and viruses share common features: size, structure, biogenesis and uptake. In order to generate EVs expressing the SARS-CoV-2 spike protein on their surface (S-EVs), we collected EVs from SARS-CoV-2 spike expressing human embryonic kidney (HEK-293T) cells by stable transfection with a vector coding for the S1 and S2 subunits. S-EVs were characterized using nanoparticle tracking analysis, ExoView and super-resolution microscopy. We obtained a population of EVs of 50 to 200 nm in size. Spike expressing EVs represented around 40% of the total EV population and co-expressed spike protein with tetraspanins on the surfaces of EVs. We subsequently used ACE2-positive endothelial and bronchial epithelial cells for assessing the internalization of labeled S-EVs using a cytofluorimetric analysis. Internalization of S-EVs was higher than that of control EVs from non-transfected cells. Moreover, S-EV uptake was significantly decreased by anti-ACE2 antibody pre-treatment. Furthermore, colchicine, a drug currently used in clinical trials, significantly reduced S-EV entry into the cells. S-EVs represent a simple, safe, and scalable model to study host-virus interactions and the mechanisms of novel therapeutic drugs.
MeSH term(s)	Angiotensin-Converting Enzyme 2/immunology ; Antibodies, Blocking/pharmacology ; COVID-19/metabolism ; COVID-19/virology ; Cell Line ; Cells, Cultured ; Colchicine/pharmacology ; Extracellular Vesicles/metabolism ; Flow Cytometry/methods ; HEK293 Cells ; Host Microbial Interactions/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/virology ; Humans ; Microscopy, Fluorescence/methods ; Protein Binding/drug effects ; SARS-CoV-2/metabolism ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Antibodies, Blocking ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Colchicine (SML2Y3J35T)
Language	English
Publishing date	2022-01-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11010146
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online ; E-Book: Procedures in cosmetic dermatology

Tanzi, Elizabeth L. / Dover, Jeffrey S. / Spring, Leah K.

lasers, lights, and energy devices

(Procedures in cosmetic dermatology)

2023

Abstract: ... L. Tanzi, Jeffrey S. Dover, and Leah K. Spring, it provides an overview of the underlying scientific ...

Author's details	edited by Elizabeth L. Tanzi, Jeffrey S. Dover, and Leah K. Spring
Series title	Procedures in cosmetic dermatology
Abstract	Offering a step-by-step, practical approach to this challenging area of dermatology, Procedures in Cosmetic Dermatology: Lasers, Lights, and Energy Devices, 5th Edition, enables you to master the up-to-date cosmetic techniques that produce the superior results your patients expect. Edited by expert clinicians Drs. Elizabeth L. Tanzi, Jeffrey S. Dover, and Leah K. Spring, it provides an overview of the underlying scientific principles of lasers and lights in dermatology, as well as the latest treatment options—all abundantly illustrated and evidence based. A substantial video library demonstrating applications and technical aspects helps you successfully incorporate the latest procedures into your practice. -- From the publisher.
Keywords	Dermatology
Subject code	733
Language	English
Size	1 online resource :, illustrations, charts, figures.
Edition	Fifth edition.
Publisher	Elsevier Inc
Publishing place	Philadelphia, PA
Document type	Book ; Online ; E-Book
Note	Includes index.
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	0-323-82906-6 ; 0-323-82905-8 ; 978-0-323-82906-9 ; 978-0-323-82905-2
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Generation of Spike-Extracellular Vesicles (S-EVs) as a Tool to Mimic SARS-CoV-2 Interaction with Host Cells

Roberta Verta / Cristina Grange / Renata Skovronova / Adele Tanzi / Licia Peruzzi / Maria Chiara Deregibus / Giovanni Camussi / Benedetta Bussolati

Cells, Vol 11, Iss 146, p

2022 Volume 146

Abstract	Extracellular vesicles (EVs) and viruses share common features: size, structure, biogenesis and uptake. In order to generate EVs expressing the SARS-CoV-2 spike protein on their surface (S-EVs), we collected EVs from SARS-CoV-2 spike expressing human embryonic kidney (HEK-293T) cells by stable transfection with a vector coding for the S1 and S2 subunits. S-EVs were characterized using nanoparticle tracking analysis, ExoView and super-resolution microscopy. We obtained a population of EVs of 50 to 200 nm in size. Spike expressing EVs represented around 40% of the total EV population and co-expressed spike protein with tetraspanins on the surfaces of EVs. We subsequently used ACE2-positive endothelial and bronchial epithelial cells for assessing the internalization of labeled S-EVs using a cytofluorimetric analysis. Internalization of S-EVs was higher than that of control EVs from non-transfected cells. Moreover, S-EV uptake was significantly decreased by anti-ACE2 antibody pre-treatment. Furthermore, colchicine, a drug currently used in clinical trials, significantly reduced S-EV entry into the cells. S-EVs represent a simple, safe, and scalable model to study host-virus interactions and the mechanisms of novel therapeutic drugs.
Keywords	extracellular vesicles ; COVID-19 ; SARS-CoV-2 ; SARS-CoV-2 spike protein ; colchicine ; anti-ACE2 ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book: Procedures in Cosmetic Dermatology: Lasers, Lights, and Energy Devices

Tanzi, Elizabeth L / Dover, Jeffrey S. / Spring, Leah K.

2022

Size	224 p.
Publisher	Elsevier - Health Sciences Division
Document type	Book
Note	PDA Manuell_19
Format	193 x 242 x 17
ISBN	9780323829052 ; 0323829058
Database	PDA

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Article ; Online: PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer’s disease risk

Karin Lopatko Lindman / Caroline Jonsson / Bodil Weidung / Jan Olsson / Janardan P. Pandey / Dmitry Prokopenko / Rudolph E. Tanzi / Göran Hallmans / Sture Eriksson / Fredrik Elgh / Hugo Lövheim

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 8

Abstract: ... for Alzheimer’s disease (AD) and is an entry co-receptor for herpes simplex virus-1. We conducted a nested case–control ...

Abstract	Abstract PILRA (rs1859788 A > G) has been suggested to be a protective variant for Alzheimer’s disease (AD) and is an entry co-receptor for herpes simplex virus-1. We conducted a nested case–control study of 360 1:1-matched AD subjects. Interactions between the PILRA-A allele, APOE risk variants (ε3/ε4 or ε4/ε4) and GM17 for AD risk were modelled. The associations were cross-validated using two independent whole-genome sequencing datasets. We found negative interactions between PILRA-A and GM17 (OR 0.72, 95% CI 0.52–1.00) and between PILRA-A and APOE risk variants (OR 0.56, 95% CI 0.32–0.98) in the discovery dataset. In the replication cohort, a joint effect of PILRA and PILRA × GM 17/17 was observed for the risk of developing AD (p .02). Here, we report a negative effect modification by PILRA on APOE and GM17 high-risk variants for future AD risk in two independent datasets. This highlights the complex genetics of AD.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Neurospheroid Arrays for In Vitro Studies of Alzheimer’s Disease

Mehdi Jorfi / Carla D’Avanzo / Rudolph E. Tanzi / Doo Yeon Kim / Daniel Irimia

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 13

Abstract: ... cultivate genetically-engineered stem cell-derived neurospheroids with familial Alzheimer’s ... of amyloid-β and phosphorylated tau, key hallmarks of Alzheimer’s disease. Overall, our in vitro model ...

Abstract	Abstract Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new interventions. Here, we generate neurospheroids from immortalized neural progenitor cells and human induced pluripotent stem cells that are uniform in size, into large-scale arrays. In proof of concept experiments, we validate the neurospheroids array as a sensitive and robust tool for screening compounds over extended time. We show that when suspended in three-dimensional extracellular matrix up to several weeks, the stem cell-derived neurospheroids display extensive neurite outgrowth and extend thick bundles of dendrites outward. We also cultivate genetically-engineered stem cell-derived neurospheroids with familial Alzheimer’s disease mutations for eight weeks in our microarray system. Interestingly, we observed robust accumulation of amyloid-β and phosphorylated tau, key hallmarks of Alzheimer’s disease. Overall, our in vitro model for engineering neurospheroid arrays is a valuable tool for studying complex neurodegenerative diseases and accelerating drug discovery.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease

Sang Su Kwak / Kevin J. Washicosky / Emma Brand / Djuna von Maydell / Jenna Aronson / Susan Kim / Diane E. Capen / Murat Cetinbas / Ruslan Sadreyev / Shen Ning / Enjana Bylykbashi / Weiming Xia / Steven L. Wagner / Se Hoon Choi / Rudolph E. Tanzi / Doo Yeon Kim

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 14

Abstract: The relationship between amyloid-β species and tau pathology in Alzheimer’s disease is not fully ...

Abstract	The relationship between amyloid-β species and tau pathology in Alzheimer’s disease is not fully understood. Here, the authors show that it is the increased ratio of amyloid-β42 and 40 isoforms drives tau pathology in 3D human neural cell culture models of the disease.
Keywords	Science ; Q
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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