Stockholm university

Research group Henrietta Nielsen's research group

Alzheimer’s disease followed by dementia with Lewy bodes is the main cause of neurodegenerative dementia. The neuropathological hallmarks for these disorders are different, but still share many similarities. In our group we investigate biological mechanisms promoting/leading to neurodegenerative dementia.

Group description

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 four 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 relates 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
  4. Identification of molecular mechanisms that drive insulin resistance and glucose hypometabolism in APOE4 carriers and patients with Alzheimer's disease

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.

 

FUNDING

 

SELECTION OF TERMINATED GRANTS last 5 years

Marcus Borgströms Stiftelse (PI), 2015-2016

Alzheimer's Association New Investigator Grant (USA) (PI), 2015-2017

VINNMER/Marie Curie Fellowship Grant (PI)2016-2018

Demensfonden (PI), 2017-2018

Åhlen-Stiftelsen (PI), 2017-2018

Marcus Borgströms Stiftelse (PI), 2017-2018

SCILIFE LAB Pilot Grant (PI), 2017-2018

 

ONGOING GRANT SUPPORT

Stiftelsen Olle Engkvist Byggmästare (PI), 2017-2019

Stiftelsen Olle Engkvist Byggmästare (PI), 2018-2020

Demensfonden (PI), 2019-2021

BrightFocus Foundation (USA) (PI), 2019-2022

Group members

Group managers

Henrietta Nielsen

Senior lecturer

Department of Biochemistry and Biophysics
HM Nielsen headshot

Members

Maja Sjödahl

PhD Student

Department of Biochemistry and Biophysics
Maja Sjödahl

Andreas Giannisis

PhD student

Department of Biochemistry and Biophysics

Research projects

Publications