Article
Biochemistry & Molecular Biology
Luana Naia, Makoto Shimozawa, Erika Bereczki, Xidan Li, Jianping Liu, Richeng Jiang, Romain Giraud, Nuno Santos Leal, Catarina Moreira Pinho, Erik Berger, Victoria Lim Falk, Giacomo Dentoni, Maria Ankarcrona, Per Nilsson
Summary: This study investigates the sequential onset of AD-like pathologies in App knock-in mice and reveals that energy metabolism is significantly altered at an early stage of pathology. As the pathology progresses, the brain shifts to a state of hypometabolism and synaptic abnormalities occur, including accumulation of synaptic vesicles and autophagosomes.
MOLECULAR PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Katarzyna M. Grochowska, Guilherme M. Gomes, Rajeev Raman, Rahul Kaushik, Liudmila Sosulina, Hiroshi Kaneko, Anja M. Oelschlegel, PingAn Yuanxiang, Irene Reyes-Resina, Gonca Bayraktar, Sebastian Samer, Christina Spilker, Marcel S. Woo, Markus Morawski, Juergen Goldschmidt, Manuel A. Friese, Steffen Rossner, Gemma Navarro, Stefan Remy, Carsten Reissner, Anna Karpova, Michael R. Kreutz
Summary: Soluble beta-amyloid peptide (A beta) causes synaptic dysfunction in early-stage Alzheimer's disease (AD) by suppressing the transcriptional activity of CREB. A beta induces nucleocytoplasmic trafficking of Jacob, which leads to transcriptional inactivation of CREB and loss of synapses. The compound Nitarsone restores CREB activity by hindering the assembly of a Jacob/LMO4/PP1 signalosome, preventing synaptic impairment and cognitive decline in mouse models of AD.
Article
Clinical Neurology
Jennifer S. Rabin, Emma Nichols, Renaud La Joie, Kaitlin B. Casaletto, Priya Palta, Kristen Dams-O'Connor, Raj G. Kumar, Kristen M. George, Claudia L. Satizabal, Julie A. Schneider, Judy Pa, Adam M. Brickman
Summary: Accumulating data suggests that cerebrovascular disease contributes to the pathophysiology and progression of Alzheimer's disease. Cerebral amyloid angiopathy, characterized by the build-up of beta-amyloid in blood vessel walls, commonly co-occurs with Alzheimer's disease in the aging brain and increases the risk of dementia. This study found that cerebral amyloid angiopathy independently or interactively influences tau deposition and cognitive decline, and tau mediates the association between cerebral amyloid angiopathy and cognitive decline.
Article
Cell Biology
Yizhou Yu, Giorgio Fedele, Ivana Celardo, Samantha H. Y. Loh, L. Miguel Martins
Summary: Alzheimer's disease is associated with changes in nicotinate and nicotinamide metabolism critical for mitochondrial function. Increasing the bioavailability of NAD(+) can protect against A beta toxicity, while supplementation of vitamin B or genetic mutations of PARP can rescue mitochondrial defects and reduce behavioral impairments in an Alzheimer's disease model. Polymorphisms in the PARP1 gene or intake of vitamin B are linked to a decrease in the risk and severity of Alzheimer's disease. Enhancing NAD(+) availability through vitamin B supplements or inhibition of NAD(+)-dependent enzymes like PARPs are potential therapies for Alzheimer's disease.
CELL DEATH & DISEASE
(2021)
Article
Neurosciences
Marcos Otero-Garcia, Sameehan U. Mahajani, Debia Wakhloo, Weijing Tang, Yue-Qiang Xue, Samuel Morabito, Jie Pan, Jane Oberhauser, Angela E. Madira, Tamara Shakouri, Yongning Deng, Thomas Allison, Zihuai He, William E. Lowry, Riki Kawaguchi, Vivek Swarup, Inma Cobos
Summary: This study investigates the relationship between Tau protein aggregation in neurofibrillary tangles (NFTs) and Alzheimer's disease (AD). Through high-throughput isolation and transcriptome profiling, the researchers found that NFT-bearing neurons show an upregulation of genes related to synaptic transmission, particularly genes involved in synaptic vesicle cycling. They also observed that mitochondrial dysfunction and oxidative phosphorylation vary among different cell types. Interestingly, the susceptibility to apoptosis and death is similar between NFT-bearing and NFT-free neurons.
Article
Biochemistry & Molecular Biology
Kakeru Chino, Naotaka Izuo, Hiroshi Noike, Kyosuke Uno, Tomoharu Kuboyama, Chihiro Tohda, Shin-Ichi Muramatsu, Atsumi Nitta
Summary: Alzheimer's disease is characterized by the deposition of amyloid beta in the brain. Overexpression of Shati/Nat8l can prevent cognitive dysfunction in AD model mice, suggesting it as a potential therapeutic target for AD.
NEUROCHEMICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Macarena de la Cueva, Desiree Antequera, Lara Ordonez-Gutierrez, Francisco Wandosell, Antonio Camins, Eva Carro, Fernando Bartolome
Summary: The amyloid cascade hypothesis is the most accepted hypothesis in Alzheimer's disease, suggesting that the accumulation of A beta protein may trigger the development of the disease. This accumulation may occur years before clinical symptoms, but it is unclear whether it is the cause or consequence of AD. However, it is known that the accumulation of A beta protein has toxic effects on brain cells. Therefore, it is important to study all possible events associated with this accumulation in order to develop new therapeutic strategies. The dysfunction of mitochondria could be an early feature of AD, associated with amyloid overload.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Huiqin Zhang, Xuefan Jiang, Lina Ma, Wei Wei, Zehui Li, Surui Chang, Jiayu Wen, Jiahui Sun, Hao Li
Summary: Synaptic dysfunction is closely related to Alzheimer's disease (AD), mainly due to the disruption caused by beta-amyloid (Aβ). Aβ disrupts glutamate receptors and mediates synaptic toxicity through multiple mechanisms. Synaptic dysfunction plays a critical role in cognitive impairment of AD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yan-Li Jia, Wei Wang, Ning Han, Hong-Liang Sun, Fang -Ming Dong, Ya-Xue Song, Rong-Fang Feng, Jian-Hua Wang
Summary: Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and β-amyloid (β-AMY) deposition are the main causes of AD. This study showed that the antioxidant peptide SS31 protected mitochondrial and synaptic function, reduced neuronal apoptosis and ROS levels, and improved behavioral deficits in early-stage AD.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Nutrition & Dietetics
Simon W. So, Kendra M. Fleming, Joshua P. Nixon, Tammy A. Butterick
Summary: Obesity, a known risk factor for Alzheimer's disease, increases microglial activation and inflammation. In this study, we found that a high fat diet led to neuroinflammation and cognitive decline in mice. The activation of brain microglia in obesity exacerbated AD pathology and increased the accumulation of amyloid beta plaques. Our results showed that a high fat diet decreased locomotor activity and increased anxiety-like behavior and behavioral despair. It also led to memory deficits and increased microgliosis and Aβ deposition in a young adult AD mouse model.
Review
Neurosciences
Leslie C. Norins
Summary: Substantial evidence supports the clinical testing of FDA-approved drugs for repurposing to treat Alzheimer's disease, including drug mechanisms of action, in vivo testing, and epidemiological data. Investigating already-approved compounds can be faster and more cost-effective than un-approved compounds in the drug pipeline. With the increasing prevalence of AD due to longer life expectancy, the lack of an effective drug for treatment is a pressing public health concern.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Luwen Wang, Mengyu Liu, Ju Gao, Amber M. Smith, Hisashi Fujioka, Jingjing Liang, George Perry, Xinglong Wang
Summary: This study demonstrates that promoting mitochondrial fusion can suppress toxic tau accumulation and associated neurodegeneration, ultimately improving cognitive function in a mouse model of tauopathy.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Immunology
Qiang Liu, Yi-Man Sun, Hui Huang, Chen Chen, Jie Wan, Lin-Hui Ma, Yin-Ying Sun, Hui-Hui Miao, Yu-Qing Wu
Summary: This study found that SIRT3 can improve postoperative cognitive dysfunction in aged mice by suppressing hippocampal neuroinflammation, and may be a promising therapeutic and diagnostic target for POCD.
JOURNAL OF NEUROINFLAMMATION
(2021)
Review
Biochemistry & Molecular Biology
Chang Youn Lee, In Soo Ryu, Jin-Hyeob Ryu, Hyun-Jeong Cho
Summary: Alzheimer's disease is a progressive neurodegenerative disorder, with miRNAs playing a crucial role in its pathological processes. Limitations of current pharmaceutical therapies have led to research on miRNA-based next-generation therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Wojciech K. Panek, David M. Murdoch, Margaret E. Gruen, Freya M. Mowat, Robert D. Marek, Natasha J. Olby
Summary: Similar neurological disorders associated with aging, such as Alzheimer's disease and canine cognitive dysfunction syndrome, have been observed in both humans and dogs. The concentrations of A beta 42 and A beta 40 in plasma increase with age in both species, but decrease in individuals with the diseases.
MOLECULAR NEUROBIOLOGY
(2021)
