Article
Geriatrics & Gerontology
Xuewen Xiao, Hui Liu, Xixi Liu, Weiwei Zhang, Sizhe Zhang, Bin Jiao
Summary: The study systematically re-evaluated APP, PSEN1, and PSEN2 variants, showing that PSEN1 carried the most prevalent pathogenic/likely pathogenic variants, emphasizing the importance of interpreting these variants with caution according to ACMG-AMP guidelines.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Neurosciences
Xuewen Xiao, Hui Liu, Lu Zhou, Xixi Liu, Tianyan Xu, Yuan Zhu, Qijie Yang, Xiaoli Hao, Yingzi Liu, Weiwei Zhang, Yafang Zhou, Junling Wang, Jinchen Li, Bin Jiao, Lu Shen, Xinxin Liao
Summary: This study suggests that non-pathogenic variants in PSEN2 and APP may be involved in the pathogenesis of AD in the Chinese population.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Clinical Neurology
Meredith M. Course, Kathryn Gudsnuk, C. Dirk Keene, Thomas D. Bird, Suman Jayadev, Paul N. Valdmanis
Summary: Course et al. performed targeted long-read isoform-sequencing of PSEN1 and PSEN2 in individuals with sporadic Alzheimer's disease, familial Alzheimer's disease with PSEN1 and PSEN2 pathogenic variants, and controls. The study revealed unique aberrant splicing of PSEN2 in sporadic Alzheimer's disease, expanding our understanding of PSEN1 and PSEN2 variants in Alzheimer's disease and suggesting novel mechanisms of Alzheimer's disease pathogenesis.
Article
Biochemistry & Molecular Biology
Heewon Bae, Kyu Hwan Shim, Jang Yoo, Young-Soon Yang, Seong Soo A. An, Min-Ju Kang
Summary: The etiology of early-onset Alzheimer's disease (EOAD) is linked to mutations in the APP, PSEN1, and PSEN2 genes, leading to alterations in the production of amyloid beta (A beta) species. A 64-year-old woman with memory decline and a family history of Alzheimer's dementia was found to have mutations in APP (rs761339914; c.G1651A; p.V551M) and PSEN2 (rs533813519; c.C505A; p.H169N). These mutations affect protein interactions and intramolecular processes, potentially influencing A beta production and causing synergistic effects when combined. Further functional studies are needed to understand the pathological effects of these double mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Jiale Gan, Hui Zhou, Chao Liu, Liangjuan Fang
Summary: This study reported a 35-year-old female with variants in both the PSEN2 and ABCA7 genes. She had a history of migraine, patent foramen ovale, spontaneous subarachnoid hemorrhage, and multiple cerebral microhemorrhages. The findings provide information for the clinical diagnosis of AD through reviewing and comparing the published variants of PSEN2 and ABCA7 in PubMed.
NEUROLOGICAL SCIENCES
(2023)
Article
Neurosciences
J. M. Wilcox, D. C. Consoli, A. A. Tienda, S. Dixit, R. A. Buchanan, J. M. May, W. P. Nobis, F. E. Harrison
Summary: Repeated low-dose kainic acid treatment triggered non-convulsive epileptiform activity in APP/PSEN1 mice, leading to memory impairment and hippocampal long-term potentiation deficits. The high excitability in Alzheimer's disease may contribute to cognitive decline independently of beta-amyloid-plaque load, especially in younger mice without plaques.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Clinical Neurology
Fran C. van Heusden, Anne M. van Nifterick, Bryan C. Souza, Arthur S. C. Franca, Ilse M. Nauta, Cornelis J. Stam, Philip Scheltens, August B. Smit, Alida A. Gouw, Ronald E. van Kesteren
Summary: Studies in mice and humans carrying APP and/or PSEN1 mutations show abnormal neurophysiological activity, but certain measures do not translate directly between species.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Kyu-Hwan Shim, Min-Ju Kang, Heewon Bae, Danyeong Kim, Jiwon Park, Seong-Soo A. An, Da-Eun Jeong
Summary: A novel PSEN2 mutation was identified in a patient with early-onset Alzheimer's disease, which may promote the pathogenesis of the disease through altered phosphorylation of presenilin and APP processing. Further functional studies are needed to clarify the pathogenicity of the mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
David C. Consoli, Lillian J. Brady, Aaron B. Bowman, Erin S. Calipari, Fiona E. Harrison
Summary: Research has shown that both ASC deficiency and AD pathology independently decrease dopamine release in the nucleus accumbens, a key area for motivation and reward behavior. Low ASC levels and APP/PSEN1 genotype contribute to decreased enzyme activity, resulting in deficits in dopaminergic neurotransmission. These findings suggest that low ASC levels may exacerbate the effects of age and disease on dopamine availability and synaptic transmission, potentially leading to behavioral changes seen in AD patients such as decreased motivation, anhedonia, and sleep disorders.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kyu Hwan Shim, Sangjoon Kang, Seong Soo A. An, Min Ju Kang
Summary: A PSEN1 gene mutation was discovered in a Korean patient with early-onset AD, suggesting its association with AD pathogenesis and the need for routine screening in this population. The mutated amino acid may destabilize gamma-secretase. In the future, a gene panel incorporating the APOE4 gene may predict AD onset and facilitate personalized treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Luming Zhuang, Chenglin Li, Fei Peng, Elleen Xue, Wenzhe Li, Xinyue Sun, Ping Chen, Qian Zhou, Lei Xue
Summary: Through studying fly AD models, it was found that inhibiting ESCRT components can improve AD-like symptoms induced by APP, suggesting the important role of ESCRT in AD pathogenesis and providing clues for alternative therapeutic strategies for AD.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Xue Wang, Yu-ting Zhu, Yi Zhu, Yan-ling Sun, Jun Huang, Zhe Li, Yan Wang, Jun-chao Wu, Zheng-hong Qin, Fang Lin
Summary: This study demonstrates that long-term running exercise can significantly alleviate cognitive dysfunction in AD mice by enhancing lysosomal function and promoting the clearance of A beta in the brain. Exercise promotes the nuclear translocation of TFEB and increases the interaction between nuclear TFEB and AMPK-mediated acetyl-CoA synthetase 2, enhancing the transcription of genes associated with lysosomal biogenesis. It also leads to increased levels of mature cathepsin D and cathepsin L, suggesting enhanced degradation of A beta peptides in activated lysosomes.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Clinical Neurology
Ove Almkvist, Charlotte Johansson, Jose Laffita-Mesa, Steinunn Thordardottir, Caroline Graff
Summary: The study aimed to investigate the effect of the APOE ε4 allele on cognitive decline in adAD. The presence of the APOE ε4 allele was found to have a positive influence on cognitive decline in APP mutation carriers and a negative influence in PSEN1 mutation carriers with adAD.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Maria Pagnon de la Vega, Carl Naslund, RoseMarie Brundin, Lars Lannfelt, Malin Lowenmark, Lena Kilander, Martin Ingelsson, Vilmantas Giedraitis
Summary: Among the 102 patients screened, two disease-causing mutations were found in PSEN1 and one in APP, along with several potentially pathogenic mutations in other genes related to neurodegenerative disorders. These findings provide important information for clinical investigation and contribute to a deeper understanding of disease mechanisms.
Article
Clinical Neurology
Yueting Chen, Peng Liu, Fei Xie, Bo Wang, Zhiru Lin, Wei Luo
Summary: A patient with a de novo mutation in PSEN1 presented with early-onset parkinsonism and mild cognitive impairment, with good response to levodopa. Brain MRI showed atrophy of the bilateral frontotemporal lobe and hippocampus. Various PET scans revealed decreased metabolism and dopamine transporter distribution in the bilateral putamen and caudate nucleus, as well as beta-amyloid protein deposition.
NEUROLOGICAL SCIENCES
(2022)