The Swedish BioFINDER study

Project: Research

Research areas and keywords

UKÄ subject classification

  • Neurology
  • Psychiatry
  • Neurosciences

Keywords

  • Alzheimer's disease, Parkinson's disease, MRI, PET, Biomarkers, Early diagnosis, Dementia, Movement disorders

Description

BioFINDER is based in Sweden and collaborates with leading scientists, universities and companies world-wide. The aim is to discover key pathological mechanisms in Alzheimer’s disease and other neurodegenerative diseases such as parkinsonian disorders.

Background
Alzheimer's disease (AD) and Parkinson's disease (PD) are major causes of disability, institutionalization and premature death in the elderly, and the costs are vast and increase dramatically worldwide. We have shown that the pathologies of AD and PD start 10-20 years before overt clinical symptoms, opening a window for early diagnosis and treatment. With novel accurate diagnostic methods we could already today initiate symptomatic treatments at an earlier stage.
Numerous clinical phase III studies have been performed evaluating new disease-modifying therapies for AD and PD, but all have yet failed. New treatments designed to stop the key disease pathologies of AD and PD will most likely only be effective if initiated during the very early stages of the diseases, before widespread and irreversible neurodegeneration has already occurred. We therefore develop diagnostic algorithms with novel biomarkers and brain imaging methods, which will be crucial for future clinical trials. Our studies will also unravel the early disease mechanisms in subjects affected by AD and PD to accelerate the development of new and effective therapies.

Purpose and aims
1) To identify and validate cost effective blood-based biomarkers to improve the diagnostics of AD- and PD-related disorders in a primary care setting.
2) To develop diagnostic algorithms including advanced brain imaging and cerebrospinal fluid biomarkers to be able to diagnose the diseases earlier and more accurately in specialized healthcare clinics.
3) To develop novel tools enabling efficient clinical trials, i.e. methods improving i) accurate patient selection, ii) relevant stratification of patient populations and iii) assessment of treatment effects on key drug targets in affected humans.
4) To investigate the underlying disease mechanisms of AD and PD in humans and to establish new disease models for human experimental research aiming at finding new relevant drug targets.

Project description
We include well-defined, clinically relevant population- and clinic-based cohorts of patients with early symptoms and healthy elderly followed longitudinally and prospectively for 6 years. We perform detailed clinical assessments and analyze the blood and cerebrospinal fluid with state-of-the-art quantitative mass spectrometry and highly sensitive immune-based approaches. Advanced high-field magnetic resonance (MR) is used to unravel the structural and functional connectivity in the brain and newly developed positron emission tomography (PET) ligands are used to detect regional tau and amyloid pathology. The project's unique strength is that clinically relevant and very well-characterized cohorts are examined with world-leading technologies in protein chemistry and brain imaging. Further, in vivo microdialyses in humans and animal models are used together with infusion of 13C-labeled leucine to further understand the mechanisms behind amyloid accumulation in these neurodegenerative disorders. We also develop novel and relevant human-derived cell models to understand disease pathology and facilitate drug discovery.

Significance
New knowledge about the molecular pathologies of AD and PD will be vital for improving the clinical diagnostic work-up and drug discovery. In the short-term perspective our results will improve the diagnostic work-up in the clinics. In the longer term, findings from our study will facilitate the development of new drugs that can halt the disease progression at the earliest stages when no disabling symptoms have yet developed.

Preliminary results
Our previous results have already been implemented into modern diagnostic criteria as well as optimized design of clinical trials in AD. For instance, our studies are part of the basis for the newly proposed diagnostic criteria for AD and were a significant part of the scientific foundation for the European Medicines Agencies (EMA) recommendation to use cerebrospinal fluid biomarkers for early detection of AD in clinical trials.
StatusActive
Effective start/end date2010/01/012022/01/01

Collaborative partners

Participants