Nielsen Lab September 2017

 
Andreas Giannisis, Erik Becher, Simon Moussaud, Henrietta Nielsen, Daniel Twohig, Kalicharan Patra
Andreas Giannisis, Erik Becher, Simon Moussaud, Henrietta Nielsen, Daniel Twohig, Kalicharan Patra
 

Research Project

Alzheimer’s disease (AD) followed by dementia with Lewy bodes is the main cause of neurodegenerative dementia. The neuropathological hallmarks for these disorders are different however they do share many similarities. Risk factors for both disorders include high age, gender and various environmental factors affected by diet, exercise and education. The APOEε4 allele is to date the strongest and most replicated genetic risk factor for sporadic late onset AD and recent studies have further demonstrated an increased risk of DLB in individuals carrying an APOEε4-allele. In contrary, the APOEε2 allele is protective against both disorders. In humans the APOE gene is polymorphic with 3 different variants (APOEε2, APOEε3, APOEε4) contrary to other mammals who only have one type. The biological mechanisms underlying the variation in risk of diseases due to APOE genotype are yet to be determined. It is well-known that individuals with an APOEε4 genotype exhibit AD-related brain pathology already at the 4th or 5th decade of life in the absence of cognitive symptoms. We have previously shown that the APOE gene product apolipoprotein E (apoE) negatively affects amyloid-β uptake in cultures of primary human glial cells (Nielsen et al 2010, Mulder et al 2014) as well as rodent cells (Fu et al 2016). Results from our recent studies also propose that APOEε4-carriers are deficient in plasma apoE due to a specific reduction of apoE4 isoform levels (Martinez-Morillo et al 2014). Whether this plasma apoE-deficiency contributes to risk of neurodegenerative disease is one of our main research areas.

In our group we investigate biological mechanisms promoting/leading to neurodegenerative dementia. Using primary human cell cultures we are investigating the cellular responses to disease-associated molecules and in brain tissues from patients with neurodegenerative dementia we are searching for disease-specific protein complexes that can be traced as biomarkers in either cerebrospinal fluid or plasma samples from patients at risk of or with neurodegenerative disease

Currently we are working on three main research topics:

  1. Whether and how alpha-synuclein relates to Alzheimer’s disease pathogenesis and pathology
  2. Whether and how the expression of different apoE variants in the periphery relate to pathological processes in the brain
  3. Which plasma and cerebrospinal fluid markers can aid identification of individuals who will develop neurodegenerative disease and which markers can aid the differential diagnosis of patients with manifest neurodegenerative dementia

In our efforts to further our understanding of processes linked to neurodegenerative disease we have for several years closely collaborated with many international colleagues and are always open to new collaborations.

Key collaborators are:

Dr. Eleftherios Diamandis and team at the Mount Sinai Hospital/Research Institute, Toronto Canada.

Dr. Linda White and team at NTNU, Trondheim Norway

Dr. Kevin Morgan and team at the University of Nottingham, Nottingham UK

Dr. Robert Veerhuis and team at the VU University medical center, Amsterdam the Netherlands

Dr. Ioannis Sotiropoulos and team at the Minho University, Braga Portugal

Dr. Pamela McLean and team, Mayo Clinic, Jacksonville FL USA

 

We gratefully enjoy current support for our research from:

VINNMER/Marie Curie Returning Grant (Sweden/EU)

Marcus Borgströms stiftelse (Sweden)

Demensfonden (Sweden)

Alzheimer’s Association (USA), Henrietta featured in Alzheimer’s Association’s Women #ENDALZ

Former students:

  • Natalia Fijol, Research trainee

  • Catharina Lotsch, Erasmus exchange student

  • Durga Inturi, Master diploma student