Article
Biochemical Research Methods
Paige E. Lawler, James G. Bollinger, Suzanne E. Schindler, Cynthia R. Hodge, Nicolas J. Iglesias, Vishal Krishnan, John B. Coulton, Iran Li, David M. Holtzman, Randall J. Bateman
Summary: Although the APOE 4 allele is highly associated with sporadic Alzheimer's disease, the mechanism of apolipoprotein (apoE) and AD pathophysiology remains unclear. This study developed a LC-MS/MS assay to measure both unmodified and O-glycosylated apoE peptides in plasma and cerebrospinal fluid (CSF). The results indicate that plasma apoE glycosylation levels correlate with total apoE levels, APOE genotype, and amyloid status, suggesting it could be a marker of brain amyloidosis and may contribute to the pathophysiology of AD.
ANALYTICAL BIOCHEMISTRY
(2023)
Article
Clinical Neurology
Cristiana J. Meuret, Yueming Hu, Sabrina Smadi, Mikaila Ann Bantugan, Haotian Xian, Ashley E. Martinez, Ronald M. Krauss, Qiu-Lan Ma, Dobrin Nedelkov, Hussein N. Yassine
Summary: Carrying the ApoE sigma 4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer's disease. The study found that apoE glycosylation in cerebrospinal fluid (CSF) correlates with CSF A beta(42) levels and small high-density lipoprotein particles (s-HDL-P), indicating a potential role of apoE glycosylation in influencing brain A beta metabolism.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Clinical Neurology
Andreas Giannisis, Asma Al-Grety, Henrik Carlsson, Kalicharan Patra, Daniel Twohig, Sigrid Botne Sando, Camilla Lauridsen, Guro Berge, Goril Rolfseng Grontvedt, Geir Brathen, Linda R. White, Kim Kultima, Henrietta M. Nielsen
Summary: This study found important associations between low plasma apoE levels and increased risk of Alzheimer's disease (AD), as well as progression from mild cognitive impairment to a clinical AD diagnosis.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Clinical Neurology
Madia Lozupone, Bruno Pietro Imbimbo, Claudia Balducci, Filomena Lo Vecchio, Paola Bisceglia, Raffaela Rita Latino, Maurizio Leone, Vittorio Dibello, Vincenzo Solfrizzi, Antonio Greco, Antonio Daniele, Mark Watling, Davide Seripa, Francesco Panza
Summary: This article discusses the role of human apolipoprotein E (apoE) in the pathophysiology of Alzheimer's disease (AD), describing its impact on brain homeostasis, neuroinflammation, blood-brain barrier permeability, glial function, synaptogenesis, oral/gut microbiota, neural networks, amyloid beta deposition, and tau-mediated neurodegeneration. It also provides updates on different therapeutic approaches targeting apoE in AD treatment.
ALZHEIMERS & DEMENTIA
(2023)
Review
Neurosciences
Huaxue Xu, Jiajia Fu, Risna Begam Mohammed Nazar, Jing Yang, Sihui Chen, Yan Huang, Ting Bao, Xueping Chen
Summary: Prior studies have shown conflicting findings on the association between apolipoprotein E (APOE)-epsilon 4 and serum lipids in Alzheimer's disease (AD) patients and healthy individuals. Our comprehensive study found that individuals with the APOE epsilon 4 allele had higher levels of total cholesterol (TC) and low-density lipoprotein (LDL) compared to non-carriers. There were no significant differences in high-density lipoprotein (HDL) and triglyceride (TG) levels between APOE epsilon 4 allele carriers and non-carriers. Importantly, elevated TC and LDL levels varied significantly between AD patients and healthy controls. A network meta-analysis did not find a distinct effect of carrying one or two APOE epsilon 4 alleles on lipid profiles. Higher TC and LDL levels were more pronounced in APOE epsilon 4 allele carriers with AD than in healthy controls.
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
Neurosciences
Yen Ying Lim, Matthew P. Pase, Rachel F. Buckley, Nawaf Yassi, Lisa Bransby, Christopher Fowler, Simon M. Laws, Colin L. Masters, Paul Maruff
Summary: The study found that middle-aged adults with the APOE ε4 homozygous genotype exhibit memory impairment, which increases with age, while middle-aged adults with the APOE ε4 heterozygous genotype do not show significant differences in cognition compared to non-carriers.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Alexander P. Gabrielli, Ian Weidling, Amol Ranjan, Xiaowan Wang, Lesya Novikova, Subir Roy Chowdhury, Blaise Menta, Alexandra Berkowicz, Heather M. Wilkins, Kenneth R. Peterson, Russell H. Swerdlow
Summary: Mitochondrial dysfunction can activate APOE expression by altering transcription factors and stress signaling pathways, thereby influencing the biology of the APOE gene and apoE protein.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Chemistry, Multidisciplinary
Dylan Mah, Yanan Zhu, Guowei Su, Jing Zhao, Ashely Canning, James Gibson, Xuehong Song, Eduardo Stancanelli, Yongmei Xu, Fuming Zhang, Robert J. Linhardt, Jian Liu, Lianchun Wang, Chunyu Wang
Summary: Apolipoprotein E (ApoE)'s epsilon 4 allele is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Heparan sulfate (HS) on the cell surface acts as a cofactor for the interaction between ApoE and LRP1, as well as the prion-like spread of tau pathology between cells. 3-O-sulfated HS has been linked to AD through its interaction with tau, and increased levels of 3-O-sulfated HS and 3-O-sulfotransferases have been observed in the AD brain. This study characterizes the interactions between ApoE and HS in different ApoE isoforms, and suggests that the interplay between 3-O-sulfated HS, tau, and ApoE isoforms may modulate AD risk.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Timo Eninger, Stephan A. Mueller, Mehtap Bacioglu, Manuel Schweighauser, Marius Lambert, Luis F. Maia, Jonas J. Neher, Sarah M. Hornfeck, Ulrike Obermueller, Gernot Kleinberger, Christian Haass, Philipp J. Kahle, Matthias Staufenbiel, Lingyan Ping, Duc M. Duong, Allan Levey, Nicholas T. Seyfried, Stefan F. Lichtenthaler, Mathias Jucker, Stephan A. Kaeser
Summary: Single-cell transcriptomics has revealed glial activation states associated with neurodegenerative diseases, but little is known about biomarker changes in bodily fluids. This study explored proteomic changes in cerebrospinal fluid related to proteopathic lesions in mouse models and found increased glial-derived proteins that could also be detected in human cerebrospinal fluid, supporting efforts to identify fluid biomarkers for neurodegenerative diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Neurosciences
Yanhui Zhang, Huiling Gao, Wei Zheng, He Xu
Summary: Alzheimer's disease is the most common type of dementia in elderly individuals, and there is currently no effective disease-modifying treatment. Imbalance in brain metal ions has been found to be closely related to the onset and progression of Alzheimer's disease. Recent evidence suggests that interactions between brain metal ions and apolipoprotein E may be one of the mechanisms for neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemical Research Methods
Lasse Bach Steffensen, Jannik Hjortshoj Larsen, Didde Riisager Hansen, Thi My Linh Tha, Niels Stromvig Larsen, Hans Christian Beck, Lars Melholt Rasmussen, Martin Overgaard
Summary: This article describes the development and application of a high-throughput, low-cost mass spectrometry assay for simultaneous relative quantification of nine apolipoproteins in mouse plasma. The assay enables in-depth characterization of apolipoprotein distribution across lipoprotein species and quantification of apolipoprotein deposition in mouse atherosclerotic plaques.
JOURNAL OF PROTEOME RESEARCH
(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)
Article
Psychiatry
Minghui Li, Xuhan Yang, Liya Sun, Ying Qing, Xiaowen Hu, Jie Jiang, Dandan Wang, Gaoping Cui, Yan Gao, En Zhang, Juan Zhang, Yong Yang, Chunling Wan
Summary: Recent evidence suggests a connection between lipid metabolism dysfunction and schizophrenia pathology, prompting the search for blood-based biomarkers. A study identified serum apolipoprotein A4 (ApoA4) as a potential novel biomarker for schizophrenia, with other proteins like ApoF, AGT, and ACT showing significant differences between patients and healthy controls. These findings may expand the pool of biomarker candidates for schizophrenia and shed light on the disease's underlying mechanisms.
JOURNAL OF PSYCHIATRIC RESEARCH
(2021)
Review
Clinical Neurology
Xiao-Yu Ji, Xin-Yuan Peng, Hai-Liang Tang, Hui Pan, Wei-Tang Wang, Jie Wu, Jian Chen, Nai-Li Wei
Summary: The APOE4 gene variant is the most significant genetic risk factor for Alzheimer's disease, promoting its initiation and progression. The high affinity of the APOE4 allele to triglycerides and cholesterol, leading to differences in lipid metabolism, has a widespread impact on neurons, microglia, and astrocytes. Phenotypic classification of Alzheimer's patients based on APOE4 carrier status is hypothesized to aid research, diagnosis, and treatment, as it has been found to have phenotypic differences and varied responses to treatment.
