Review
Pharmacology & Pharmacy
Benjamin R. Troutwine, Laylan Hamid, Colton R. Lysaker, Taylor A. Strope, Heather M. Wilkins
Summary: Genetic variation in the APOE gene is associated with the risk of Alzheimer's disease. The APOE epsilon 4 alleles are the strongest genetic risk factor for late onset sporadic AD, while the APOE epsilon 2 alleles have lower risk and the APOE epsilon 3 alleles have neutral risk.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Chemistry, Multidisciplinary
Shanshan Zhang, Sajid Asghar, Chenqi Zhu, Junxiu Ye, Ling Lin, Liu Xu, Ziyi Hu, Zhipeng Chen, Feng Shao, Yanyu Xiao
Summary: This study presents a multi-functional delivery system (APND-3) designed to address the issues of poor drug delivery to the brain in Alzheimer's disease (AD) treatment. The system, based on a novel peptide (MOP) with self-assembling properties, significantly enhances the delivery of MOP to the brain, reducing A beta deposition and improving neurological outcomes in AD model mice.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Biochemistry & Molecular Biology
Amanda B. Chai, Hin Hei Julian Lam, Maaike Kockx, Ingrid C. Gelissen
Summary: Research has shown a strong correlation between apoE4 and the risk of Alzheimer's disease, primarily due to increased brain Aβ burden, earlier disease onset, and worse clinical outcomes caused by apoE4. However, there is still debate on the effects of different apoE isoforms on various stages of the Aβ processing pathway, potentially reflecting inconsistencies in research methodologies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Review
Biochemistry & Molecular Biology
Kseniia S. Orobets, Andrey L. Karamyshev
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with age or inherited mutations. It is characterized by severe dementia that affects memory, cognitive functions, and daily life. The disease is linked to the accumulation of cytotoxic amyloid beta and hyperphosphorylated tau protein, as well as other pathological features. Various treatment options, such as antibody-based therapy and stem cell transplantation, are being investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Geriatrics & Gerontology
Jinsu Park, Meenu Madan, Srinivasulu Chigurupati, Seung Hyun Baek, Yoonsuk Cho, Mohamed R. Mughal, Amin Yu, Sic L. Chan, Jogi Pattisapu, Mark P. Mattson, Dong-Gyu Jo
Summary: AQP1 levels are elevated in the cerebral cortex during the early stages of AD, particularly in vulnerable neurons, and increase as aging progresses in AD mouse models. AQP1 appears to reduce A beta production by inhibiting the binding between BACE1 and APP.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Review
Neurosciences
Rebecca M. C. Gabriele, Emily Abel, Nick C. Fox, Selina Wray, Charles Arber
Summary: Amyloid precursor protein (APP) and its cleavage fragment Amyloid-beta (A beta) play crucial roles in Alzheimer's disease (AD). Genetic alterations that increase the overall dosage of APP or favor the generation of more aggregation-prone A beta species directly contribute to the disease. Lowering APP expression is an attractive approach for AD treatment and prevention. New technologies that reduce APP expression may offer disease modification and slow clinical progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medical Laboratory Technology
Kristopher M. Kirmess, Matthew R. Meyer, Mary S. Holubasch, Stephanie S. Knapik, Yan Hu, Erin N. Jackson, Scott E. Harpstrite, Philip B. Verghese, Tim West, Ilana Fogelman, Joel B. Braunstein, Kevin E. Yarasheski, John H. Contois
Summary: The PrecivityAD (TM) test developed by C2N quantifies A beta isoforms and APOE isoform-specific proteotyping accurately and with high precision. The results show that the test is sensitive, linear over a wide analytical range, free from significant interferences, and suitable for use in clinical laboratories.
CLINICA CHIMICA ACTA
(2021)
Article
Neurosciences
Dongjie Hu, Xiangjun Dong, Qunxian Wang, Mingjing Liu, Shuyue Luo, Zijun Meng, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: This study explores the role of Purkinje cell protein 4 (PCP4) in the progression of Alzheimer's disease (AD). PCP4 overexpression affects the processing of amyloid-beta protein precursor (AβPP) and promotes the production and deposition of amyloid-beta (Aβ). It also exacerbates learning and memory impairment in AD model mice. PCP4 may serve as a potential therapeutic target for AD by targeting Aβ pathology.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Review
Endocrinology & Metabolism
Yanjun Guo, Qinqiu Wang, Shenghui Chen, Chengfu Xu
Summary: This article summarizes the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues, indicating that peptides generated by non-amyloidogenic processing can have positive effects on metabolism, while those produced by amyloidogenic processing may have negative impacts. Abnormal expression of APP is associated with metabolic diseases (such as diabetes, obesity, etc.) and cancer.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Geriatrics & Gerontology
Kenji Yamamoto, Ryo Yamamoto, Nobuo Kato
Summary: In this study, it was found that specific antibodies can recover the activity of BK channels suppressed by Aβ oligomers in neurons of Alzheimer's disease model mice, suggesting an important role of APP in this process.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Review
Neurosciences
Xi-Jun Song, He-Yan Zhou, Yu-Ying Sun, Han-Chang Huang
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles. The main constituent of senile plaques, Aβ peptide, is derived from AβPP through cleaving by enzymes. Post-translational modifications like phosphorylation and glycosylation of AβPP may affect its trafficking and cleavage.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Christophe Mesangeau, Pascal Carato, Nicolas Renault, Mathilde Coevoet, Paul-Emmanuel Larchanche, Amelie Barczyk, Luc Buee, Nicolas Sergeant, Patricia Melnyk
Summary: This paragraph discusses the rationale and methods for selecting small drug compounds based on structure-activity relationships. It also describes the various screening parameters used to identify compounds with potential anti-Alzheimer activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ryota Suzuki, Haruka Takahashi, Chika Yoshida, Masafumi Hidaka, Tomohisa Ogawa, Eugene Futai
Summary: In this study, the APP mutation T714I, which is associated with familial Alzheimer's disease, was found to severely reduce the cleavage of A beta. Secondary mutations were identified that restored the cleavage of APP T714I and could modulate the production of A beta species in mammalian cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Min Kim, Alejo Nevado-Holgado, Luke Whiley, Stuart G. Snowden, Hilkka Soininen, Iwona Kloszewska, Patrizia Mecocci, Magda Tsolaki, Bruno Vellas, Madhav Thambisetty, Richard J. B. Dobson, John E. Powell, Michelle K. Lupton, Andy Simmons, Latha Velayudhan, Simon Lovestone, Petroula Proitsi, Cristina Legido-Quigley
JOURNAL OF ALZHEIMERS DISEASE
(2017)
Article
Neurosciences
Ivan Koychev, Roger N. Gunn, Azadeh Firouzian, Jennifer Lawson, Giovanna Zamboni, Basil Ridha, Barbara J. Sahakian, James B. Rowe, Alan Thomas, Lynn Rochester, Dominic Ffytche, Robert Howard, Henrik Zetterberg, Clare MacKay, Simon Lovestone
JOURNAL OF ALZHEIMERS DISEASE
(2017)
Article
Neurosciences
Wasim Khan, Vincent Giampietro, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Christian Buechel, Patricia Conrod, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Anreas Heinz, Bernd Ittermann, Herve Lemaitre, Frauke Nees, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Michael N. Smolka, Andreas Stroehle, Jeurgen Gallinat, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Magda Tsolaki, Patrizia Mecocci, Christian Spenger, Victor L. Villemagne, Colin L. Masters, J-Sebastian Muehlboeck, Lars Backman, Laura Fratiglioni, Gregoria Kalpouzos, Lars-Olof Wahlund, Gunther Schumann, Simon Lovestone, Steven C. R. Williams, Eric Westman, Andrew Simmons
JOURNAL OF ALZHEIMERS DISEASE
(2017)
Article
Neurosciences
Michelle K. Lupton, Beben Benyamin, Petroula Proitsi, Dale R. Nyholt, Manuel A. Ferreira, Grant W. Montgomery, Andrew C. Heath, Pamela A. Madden, Sarah E. Medland, Scott D. Gordon, Simon Lovestone, Magda Tsolaki, Iwona Kloszewska, Hilkka Soininen, Patrizia Mecocci, Bruno Vellas, John F. Powell, Ashley I. Bush, Margaret J. Wright, Nicholas G. Martin, John B. Whitfield
JOURNAL OF ALZHEIMERS DISEASE
(2017)
Article
Geriatrics & Gerontology
Emrin Horgusluoglu-Moloch, Kwangsik Nho, Shannon L. Risacher, Sungeun Kim, Tatiana Foroud, Leslie M. Shaw, John Q. Trojanowski, Paul S. Aisen, Ronald C. Petersen, Clifford R. Jack, Simon Lovestone, Andrew Simmons, Michael W. Weiner, Andrew J. Saykin
NEUROBIOLOGY OF AGING
(2017)
Article
Clinical Neurology
Danielle Gunn-Moore, Oksana Kaidanovich-Beilin, Maria Carolina Gallego Iradi, Frank Gunn-Moore, Simon Lovestone
ALZHEIMERS & DEMENTIA
(2018)
Article
Clinical Neurology
Rebecca G. Smith, Eilis Hannon, Philip L. De Jager, Lori Chibnik, Simon J. Lott, Daniel Condliffe, Adam R. Smith, Vahram Haroutunian, Claire Troakes, Safa Al-Sarraj, David A. Bennett, John Powell, Simon Lovestone, Leonard Schalkwyk, Jonathan Mill, Katie Lunnon
ALZHEIMERS & DEMENTIA
(2018)
Review
Neurosciences
Liu Shi, Alison L. Baird, Sarah Westwood, Abdul Hye, Richard Dobson, Madhav Thambisetty, Simon Lovestone
JOURNAL OF ALZHEIMERS DISEASE
(2018)
Article
Neurosciences
Riona Mc Ardle, Rosie Morris, Aodhan Hickey, Silvia Del Din, Ivan Koychev, Roger N. Gunn, Jennifer Lawson, Giovanna Zamboni, Basil Ridha, Barbara J. Sahakian, James B. Rowe, Alan Thomas, Henrik Zetterberg, Clare MacKay, Simon Lovestone, Lynn Rochester
JOURNAL OF ALZHEIMERS DISEASE
(2018)
Article
Genetics & Heredity
Antonio F. Pardinas, Peter Holmans, Andrew J. Pocklington, Valentina Escott-Price, Stephan Ripke, Noa Carrera, Sophie E. Legge, Sophie Bishop, Darren Cameron, Marian L. Hamshere, Jun Han, Leon Hubbard, Amy Lynham, Kiran Mantripragada, Elliott Rees, James H. MacCabe, Steven A. McCarroll, Bernhard T. Baune, Gerome Breen, Enda M. Byrne, Udo Dannlowski, Thalia C. Eley, Caroline Hayward, Nicholas G. Martin, Andrew M. McIntosh, Robert Plomin, David J. Porteous, Naomi R. Wray, Armando Caballero, Daniel H. Geschwind, Laura M. Huckins, Douglas M. Ruderfer, Enrique Santiago, Pamela Sklar, Eli A. Stahl, Hyejung Won, Esben Agerbo, Thomas D. Als, Ole A. Andreassen, Marie Baekvad-Hansen, Preben Bo Mortensen, Carsten Bocker Pedersen, Anders D. Borglum, Jonas Bybjerg-Grauholm, Srdjan Djurovic, Naser Durmishi, Marianne Giortz Pedersen, Vera Golimbet, Jakob Grove, David M. Hougaard, Manuel Mattheisen, Espen Molden, Ole Mors, Merete Nordentoft, Milica Pejovic-Milovancevic, Engilbert Sigurdsson, Teimuraz Silagadze, Christine Soholm Hansen, Kari Stefansson, Hreinn Stefansson, Stacy Steinberg, Sarah Tosato, Thomas Werge, David A. Collier, Dan Rujescu, George Kirov, Michael J. Owen, Michael C. O'Donovan, James T. R. Walters
Article
Geriatrics & Gerontology
Konstantinos Poulakis, Joana B. Pereira, Patrizia Mecocci, Bruno Vellas, Magda Tsolaki, Iwona Kloszewska, Hilkka Soininen, Simon Lovestone, Andrew Simmons, Lars-Olof Wahlund, Eric Westman
NEUROBIOLOGY OF AGING
(2018)
Article
Radiology, Nuclear Medicine & Medical Imaging
Azadeh Firouzian, Alex Whittington, Graham E. Searle, Ivan Koychev, Giovanna Zamboni, Simon Lovestone, Roger N. Gunn
Correction
Neurosciences
Claudie Hooper, Ricardo Sainz-Fuertes, Steven Lynham, Abdul Hye, Richard Killick, Alice Warley, Cecilia Bolondi, Jennifer Pocock, Simon Lovestone
Article
Behavioral Sciences
Adam Strzelczyk, Angel Aledo-Serrano, Antonietta Coppola, Adrien Didelot, Elizabeth Bates, Ricardo Sainz-Fuertes, Charlotte Lawthom
Summary: Epilepsy is a serious neurological disorder that significantly impacts the lives of people with this condition. A survey conducted in five European countries aimed to understand the burden of epilepsy and its treatment on the quality of life of individuals with epilepsy.
EPILEPSY & BEHAVIOR
(2023)
Article
Behavioral Sciences
Charlotte Lawthom, Adrien Didelot, Antonietta Coppola, Angel Aledo-Serrano, Barbara Fazekas, Ricardo Sainz-Fuertes, Adam Strzelczyk
Summary: This study assessed the impact of epilepsy and antiseizure medications (ASMs) on sleep quality in people with epilepsy. The results showed that people with epilepsy had worse sleep quality, and some ASMs contributed to poorer sleep. Sleep quality was correlated with quality of life and physical and mental health.
EPILEPSY & BEHAVIOR
(2023)