University of Oulu

Leal, N., Dentoni, G., Schreiner, B., Kämäräinen, O., Partanen, N., Herukka, S., Koivisto, A., Hiltunen, M., Rauramaa, T., Leinonen, V., Ankarcrona, M. (2018) Alterations in mitochondria-endoplasmic reticulum connectivity in human brain biopsies from idiopathic normal pressure hydrocephalus patients. Acta Neuropathologica Communications, 6 (1), 102. doi:10.1186/s40478-018-0605-2

Alterations in mitochondria-endoplasmic reticulum connectivity in human brain biopsies from idiopathic normal pressure hydrocephalus patients

Saved in:
Author: Leal, Nuno Santos1; Dentoni, Giacomo1; Schreiner, Bernadette1;
Organizations: 1Center for Alzheimer Research, Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet
2Institute of Clinical Medicine – Neurosurgery, University of Eastern Finland
3Department of Neurosurgery, Kuopio University Hospital
4Institute of Clinical Medicine – Neurology, University of Eastern Finland
5Department of Neurology, Kuopio University Hospital
6Institute of Biomedicine, University of Eastern Finland
7Institute of Clinical Medicine – Pathology, University of Eastern Finland
8Department of Pathology, Kuopio University Hospital
9Unit of Clinical Neuroscience, Neurosurgery, University of Oulu
10Medical Research Center, Oulu University Hospital
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2018111247864
Language: English
Published: Springer Nature, 2018
Publish Date: 2018-11-12
Description:

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropathology with unknown cause characterised by gait impairment, cognitive decline and ventriculomegaly. These patients often present comorbidity with Alzheimer’s disease (AD), including AD pathological hallmarks such as amyloid plaques mainly consisting of amyloid β-peptide and neurofibrillary tangles consisting of hyperphosphorylated tau protein. Even though some of the molecular mechanisms behind AD are well described, little is known about iNPH. Several studies have reported that mitochondria-endoplasmic reticulum contact sites (MERCS) regulate amyloid β-peptide metabolism and conversely that amyloid β-peptide can influence the number of MERCS. MERCS have also been shown to be dysregulated in several neurological pathologies including AD.

In this study we have used transmission electron microscopy and show, for the first time, several mitochondria contact sites including MERCS in human brain biopsies. These unique human brain samples were obtained during neurosurgery from 14 patients that suffer from iNPH. Three of these 14 patients presented comorbidities with other dementias: one patient with AD, one with AD and vascular dementia and one patient with Lewy body dementia. Furthermore, we report that the numbers of MERCS are increased in biopsies obtained from patients diagnosed with dementia. Moreover, the presence of both amyloid plaques and neurofibrillary tangles correlates with decreased contact length between endoplasmic reticulum and mitochondria, while amyloid plaques alone do not seem to affect endoplasmic reticulum-mitochondria apposition. Interestingly, we report a significant positive correlation between the number of MERCS and ventricular cerebrospinal fluid amyloid β-peptide levels, as well as with increasing age of iNPH patients.

see all

Series: Acta neuropathologica communications
ISSN: 2051-5960
ISSN-E: 2051-5960
ISSN-L: 2051-5960
Volume: 6
Issue: 1
Article number: 102
DOI: 10.1186/s40478-018-0605-2
OADOI: https://oadoi.org/10.1186/s40478-018-0605-2
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3112 Neurosciences
3124 Neurology and psychiatry
Subjects:
MAM
Tau
Funding: These studies were supported grants from: Gun and Bertil Stohne’s Foundation, Gamla Tjänarinnor Foundation, Swedish Dementia Foundation, The Foundation for Geriatric Diseases at Karolinska Institutet and Kuopio University Hospital VTR Fund. Karolinska Institutet Doctoral Grant and Gun och Bertil Stohne’s Research Stipend to NSL, and Marie Skłodowska Curie ITN grant SyDAD to GD.
Copyright information: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
  https://creativecommons.org/licenses/by/4.0/