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Leal et al. Acta Neuropathologica Communications (2018) 6:102 https://doi.org/10.1186/s40478-018-0605-RESEARCHOpen AccessAlterations in mitochondria-endoplasmic reticulum connectivity in human brain biopsies from idiopathic standard stress hydrocephalus patientsNuno Santos Leal1, Giacomo Dentoni1, Bernadette Schreiner1, Olli-Pekka K nen2,3, Nelli Partanen2,three, Sanna-Kaisa Herukka4,five, Anne M Koivisto4,five, Mikko Hiltunen6, Tuomas Rauramaa7,8, Ville Leinonen2,3,9,10 and Maria Ankarcrona1*AbstractIdiopathic normal stress hydrocephalus (iNPH) is usually a neuropathology with unknown lead to characterised by gait impairment, cognitive decline and ventriculomegaly. These individuals often present comorbidity with Alzheimer’s disease (AD), which includes AD pathological hallmarks such as amyloid plaques mainly consisting of amyloid -peptide and neurofibrillary HTRA2/OMI Protein C-6His tangles consisting of hyperphosphorylated tau protein. Although a few of the molecular mechanisms behind AD are well described, small is identified about iNPH. Quite a few studies have reported that mitochondria-endoplasmic reticulum make contact with web-sites (MERCS) regulate amyloid -peptide metabolism and conversely that amyloid -peptide can influence the number of MERCS. MERCS have also been shown to become dysregulated in a number of neurological pathologies like AD. In this study we’ve used transmission electron microscopy and show, for the first time, a number of mitochondria make contact with websites which includes MERCS in human brain biopsies. These special human brain samples had been obtained for the duration of neurosurgery from 14 individuals that endure from iNPH. Three of these 14 individuals presented comorbidities with other dementias: a single patient with AD, one particular with AD and vascular dementia and one patient with Lewy body dementia. In addition, we report that the numbers of MERCS are enhanced in biopsies obtained from individuals diagnosed with dementia. Furthermore, the presence of each amyloid plaques and neurofibrillary tangles correlates with decreased contact length involving endoplasmic reticulum and mitochondria, although amyloid plaques alone don’t appear to impact endoplasmic reticulum-mitochondria apposition. Interestingly, we report a substantial positive correlation in between the number of MERCS and ventricular cerebrospinal fluid amyloid -peptide levels, too as with increasing age of iNPH patients. Keywords and phrases: Brain biopsies, iNPH, Amyloid -peptide, Tau, MERCS, MAM.