University of Oulu

Marttinen M, Takalo M, Natunen T, Wittrahm R, Gabbouj S, Kemppainen S, Leinonen V, Tanila H, Haapasalo A and Hiltunen M (2018) Molecular Mechanisms of Synaptotoxicity and Neuroinflammation in Alzheimer’s Disease. Front. Neurosci. 12:963. doi: 10.3389/fnins.2018.00963

Molecular mechanisms of synaptotoxicity and neuroinflammation in Alzheimer’s disease

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Author: Marttinen, Mikael1; Takalo, Mari1; Natunen, Teemu1;
Organizations: 1Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
2Institute of Clinical Medicine – Neurosurgery, University of Eastern Finland, Kuopio, Finland
3Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland
4Unit of Clinical Neuroscience, Neurosurgery, University of Oulu, Oulu, Finland
5Medical Research Center, Oulu University Hospital, Oulu, Finland
6A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
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Language: English
Published: Frontiers Media, 2018
Publish Date: 2021-03-08


Alzheimer’s disease (AD) is the most common neurodegenerative disorder, which is clinically associated with a global cognitive decline and progressive loss of memory and reasoning. According to the prevailing amyloid cascade hypothesis of AD, increased soluble amyloid-β (Aβ) oligomer levels impair the synaptic functions and augment calcium dyshomeostasis, neuroinflammation, oxidative stress as well as the formation of neurofibrillary tangles at specific brain regions. Emerging new findings related to synaptic dysfunction and initial steps of neuroinflammation in AD have been able to delineate the underlying molecular mechanisms, thus reinforcing the development of new treatment strategies and biomarkers for AD beyond the conventional Aβ- and tau-targeted approaches. Particularly, the identification and further characterization of disease-associated microglia and their RNA signatures, AD-associated novel risk genes, neurotoxic astrocytes, and in the involvement of complement-dependent pathway in synaptic pruning and loss in AD have set the outstanding basis for further preclinical and clinical studies. Here, we discuss the recent development and the key findings related to the novel molecular mechanisms and targets underlying the synaptotoxicity and neuroinflammation in AD.

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Series: Frontiers in neuroscience
ISSN: 1662-4548
ISSN-E: 1662-453X
ISSN-L: 1662-4548
Volume: 12
Article number: 963
DOI: 10.3389/fnins.2018.00963
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3112 Neurosciences
Funding: This study was supported by Academy of Finland (Nos. 307866, 315459, and 288659), Sigrid Jusélius Foundation, the Strategic Neuroscience Funding of the University of Eastern Finland, and Neurocenter Finland – AlzTrans pilot project.
Copyright information: © 2018 Marttinen, Takalo, Natunen, Wittrahm, Gabbouj, Kemppainen, Leinonen, Tanila, Haapasalo and Hiltunen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.