On this World Alzheimer’s Day, we are raising awareness on the ongoing research that seeks to unravel the mysteries behind Alzheimer’s disease. Join us in celebrating the incredible advances in this research field and outstanding scientific tools supporting discoveries on risk factors and underlying mechanisms, as well as potential treatments for Alzheimer’s.
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a decline in cognitive function and memory. Symptoms can include memory loss, confusion, language impairment, and changes in behavior and personality. It is thought to be caused by abnormal protein aggregation such as β-Amyloid plaques and tau tangles, which disrupts neuron communication, leading to their dysfunction and death. Other factors like genetics, inflammation, and lifestyle have also been studied to play a part in this complex disease.
Among many scientific methodologies, electrophysiology has been pointed out as a powerful tool to investigate various pathologies, including Alzheimer’s disease. It can measure the activity of electrically active cells, including neurons, providing key insights into their function and what happens when dysregulated.
Patch clamp is a commonly used electrophysiological technique that allows scientists to study the electrical activity of a cell by sealing a small glass pipette onto its membrane. With such approach, it is possible to intracellularly measure ion channel currents in individual isolated cells, tissue sections, or patches of cell membranes. While patch clamp is a great technique for analyzing the electrical activity of individual cells, other methods let us grasp into broader neuronal interactions, as Multi-Electrode Arrays (MEAs).
MEAs enable the simultaneous recording from multiple neurons extracellularly. This advantage allows researchers to capture activity at a network level and understand how entire populations of neurons behave together. Taking this technology a step further, High-Density MEA (HD-MEA) technology provides unparalleled spatial resolution, reaching as deep as subcellular features of single neurons. Advances in HD-MEA technology not only push the boundaries of our understanding but also pave the way for future innovations.
Today, we celebrate World Alzheimer’s Day by presenting you a collection of publications on this disease’s research, some of which highlight the powerful contribution of electrophysiology in its findings.
Review | MEAs and Alzheimer
Using multielectrode arrays to investigate neurodegenerative effects of the β-Amyloid peptide
By Steven Schulte, Manuela Gries, Anne Christmann, Karl-Herbert Schäfer, Bioelectronic Medicine, 2021
This mini-review explores how MEAs are contributing to study the impact of β-Amyloid in Alzheimer’s research. Using MEAs, researchers identified that β-Amyloid increases neuronal firing and impairs long-term potentiation, supporting its role in Alzheimer’s-related neuronal dysfunction. These results support MEAs as a valuable tool to investigate neuronal communication, among other mechanisms, in neurodegenerative diseases.
Review | Brain area function and Alzheimer
What electrophysiology tells us about Alzheimer’s disease: a window into the synchronization and connectivity of brain neurons
By Claudio Babiloni, Katarzyna Blinowska, Laura Bonanni, Andrej Cichocki, Willem De Haan, Claudio Del Percio, Bruno Dubois, Javier Escudero, Alberto Fernández, Giovanni Frisoni, Bahar Guntekin, Mihaly Hajos, Harald Hampel, Emmanuel Ifeachor, Kerry Kilborn, Sanjeev Kumar, Kristinn Johnsen, Magnus Johannsson, Jaeseung Jeong, Fiona LeBeau…Fiona Randall, Neurobiology of Aging, 2020
This review paper discusses the importance of electrophysiology in Alzheimer’s research. It highlights the advantages for the use of electrophysiological techniques in different disease study models to better understand Alzheimer’s impact on neuronal function and network connectivity.
Review | Tau role in Alzheimer
Synaptic degeneration in Alzheimer disease
By Makis Tzioras, Robert I. McGeachan, Claire S. Durrant, Tara L. Spires-Jones, Nature Reviews Neurology, 2023
In this review paper, authors shed a light over synapse and neuron loss caused by the presence of β-Amyloid and tau proteins, mechanisms being thoroughly studied in Alzheimer’s disease. The review examines how these proteins contribute to synapse degeneration, which is closely linked to cognitive decline. It also discusses the potential role of glial cells in this process and explores the emerging therapeutic strategies for AD.
Research Article | Neuronal plasticity and Alzheimer
Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis
By Peter Dongmin Sohn, Cindy Tzu-Ling Huang, Rui Yan, Li Fan, Tara E. Tracy, Carolina M. Camargo, Kelly M. Montgomery, Taylor Arhar, Sue-Ann Mok, Rebecca Freilich, Justin Baik, Manni He, Shiaoching Gong, Erik D. Roberson, Celeste M. Karch, Jason E. Gestwicki, Ke Xu, Kenneth S. Kosik, Li Gan, Neuron, 2019
This study explores how a specific mutation of the tau protein affects neuronal function. The authors found a disruption in the axonal initial segment’s cytoskeleton plasticity, which leads to an increase in neuronal activity. Abnormal accumulation of another protein, end-binding protein 3 (EB3) is implicated in this effect, shedding light on how tau mutations contribute to network dysfunction in dementia.
Research Article | Peptide role and Alzheimer
The Aβ(1–38) peptide is a negative regulator of the Aβ(1–42) peptide implicated in Alzheimer disease progression
By Maa O. Quartey, Jennifer N. K. Nyarko, Jason M. Maley, Jocelyn R. Barnes, Maria A. C. Bolanos, Ryan M. Heistad, Kaeli J. Knudsen, Paul R. Pennington, Josef Buttigieg, Carlos E. De Carvalho, Scot C. Leary, Matthew P. Parsons, Darrell D. Mousseau, Scientific Reports, 2021
In this article, authors explore the relation between different forms of β-Amyloid peptides in Alzheimer’s disease, focusing on Aβ(1-38), Aβ(1-40), and Aβ(1-42). The study shows unique interactions between Aβ(1-38) and Aβ(1-40) and Aβ(1-42), with Aβ(1-38) interfering with the formation of β-sheet-rich aggregates, a trait of Alzheimer’s. Such findings bring new insights into Aβ(1-38) potential therapeutic role in Alzheimer’s research.
Research Article | Genetic risk factors and Alzheimer
Alzheimer’s genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner
By Fanny Eysert, Audrey Coulon, Emmanuelle Boscher, Anaїs-Camille Vreulx, Amandine Flaig, Tiago Mendes, Sandrine Hughes, Benjamin Grenier-Boley, Xavier Hanoulle, Florie Demiautte, Charlotte Bauer, Mikael Marttinen, Mari Takalo, Philippe Amouyel, Shruti Desai, Ian Pike, Mikko Hiltunen, Frédéric Chécler, Mélissa Farinelli, Charlotte Delay, Nicolas Malmanche, Sébastien S. Hébert, Julie Dumont, Devrim Kilinc, Jean-Charles Lambert, Julien Chapuis, Molecular Psychiatry, 2020
The study examines how Alzheimer’s is linked to the regulation of amyloid precursor protein (APP) metabolism. It identified identifies FERMT2 (Kindlin-2) as a critical factor in modulating axon guidance, which is connected to APP metabolism. FERMT2 interacts directly with APP, affecting axonal growth, synaptic connections, and long-term potentiation—all influenced by APP. Such findings shed a light on FERMT2’s role in neuronal function and its potential relevance in Alzheimer’s.
Research Article | Inflammation and Alzheimer
Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice
By Henna Jäntti, Minna Oksanen, Pinja Kettunen, Stella Manta, Lionel Mouledous , Hennariikka Koivisto, Johanna Ruuth, Kalevi Trontti, Hiramani Dhungana, Meike Keuters, Isabelle Weert, Marja Koskuvi, Iiris Hovatta , Anni-Maija Linden, Claire Rampon, Tarja Malm, Heikki Tanila, Jari Koistinaho, Taisia Rolova, Cells, 2022
In this study, the authors explore the impact of PSEN1 protein-specific mutation (ΔE9) in Alzheimer’s disease. Transplanting glial progenitors with this mutation in a disease animal model improved spatial learning and memory, accompanied by reduced human Aβ42 in the brain. Together, the presence of PSEN1 ΔE9 mutant glia led to beneficial effects on the study aged brains, such influenced by multiple factors.
Research Article | Therapeutic Targeting
Pharmacologic inhibition of LIMK1 provides dendritic spine resilience against β-amyloid
By Benjamin W. Henderson, Kelsey M., Raksha Ramdas, Courtney K. Walker, Tejeshwar C. Rao, Svitlana V. Bach, Kendall A. Curtis, Jeremy J. Day, Alexa L. Mattheyses, and Jeremy H. Herskowitz
This research article investigates a new approach to Alzheimer’s disease therapy, focusing on dendritic spine loss as a crucial factor in cognitive decline. It studies how ROCK1 and ROCK2 kinases in hippocampal neurons affect dendritic spines. On one side, ROCK1 impacts spine length, while ROCK2 leads to spine loss through LIMK1 protein. By inhibiting LIMK1, the authors were able to rescue Aβ-induced spine loss, such findings suggesting that LIMK1 inhibitor could potentially prevent dementia-related spine damage, even before symptoms manifest.