Molecular Neurobiology of Aging Unit – University of Copenhagen

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Molecular Neurobiology of Aging Unit (MNA)

MNA Unit of the BRAINlab in 2013
Publications of the NMA Unit in 2013
Detailed description of the MNA Unit

Image of brain maps of amyloid-beta accumulation in brain of patients with Alzheimer's disease, analyzed by three different method (WARM, SRTM, SUVR). Left panels: Patients. Right panels: Healthy age-matched volunteers. Note the greater differentiation observed with WARM (from Rodell et al. 2013)

  

MNA Unit of the BRAINlab in 2013

The Molecular Neurobiology of Aging Unit is a collaborative effort of the Department’s BRAINlab with the Center of Healthy Aging of the Department of Cellular and Molecular Medicine. The unit is also part and coordinator of the International Healthy Aging Network (iHAN). The network is a group of researchers affiliated with the International Alliance of Research Universities (IARU), and they collaborate and share knowledge of the characteristics of molecular and cognitive markers of healthy and unhealthy brain aging, currently focusing on the use of markers both of and beyond the amyloid-beta accumulation in the brain of patients with dementia of Alzheimer’s type, and on the mitochondrial dysfunctions that may contribute to unhealthy aging. The collaboration is heavily involved in attempts to interpret brain imaging results obtained with positron emission tomography, and engages in efforts to record signals from dysfunctional mitochondria in vivo. The current collaborators of the iHAN come from the universities in Australia (e.g., University of Queensland), the US (Yale, Hopkins, and UC Berkeley), Denmark (Aarhus and Copenhagen), and Norway (Oslo University).

There has been a dramatic rise in the interest in development of radiopharmaceuticals for the potentially important alternative pathological targets of phosphorylated tau protein aggregates in dendritic spines of neurons affected by Alzheimer’s disease. The rise is motivated by an increasing need to understand the natural history of dementia of Alzheimer’s disease type (DAT), as well as providing tools to help document the possible effects of early treatment. While the underlying mechanism of Alzheimer’s disease pathogenesis remains elusive, the focus on tauopathy, dendritic spines, monoaminergic neuromodulation, and survival of the fittest mitochondria, means that the previously popular explanation in terms of an amyloid deposition cascade now comes under intense scrutiny. This development reflects the need to examine and monitor targets such as the phosphorylated tau protein aggregates, dendritic spine receptors, exogenous agonists and antagonists, and the need to also pool the neuroimaging resources of different centers.

The diversion of the focus towards targets other than the amyloid cascade was reflected in a series of talks in November and December 2013, entitled “Beyond the Amyloid Cascade”, given by Albert Gjedde at the Lawrence Berkeley Laboratory of the University of California in Berkeley, where iHAN-trainee Adjmal Nahimi MD was hosted by Director William Jagust MD, and at the Center of Advanced Imaging at the University of Queensland in Brisbane, where iHAN-analyst Anders Rodell PhD and iHAN-trainee Michael Gejl MD currently are hosted by Director David Reutens MD, as well as at the BRAINlab. Also in November 2013, the MNA Unit hosted a visit of Professor Fahmeed Hyder PhD of Yale University, who spoke on the issue of changes of brain energy metabolism with aging.

The novel focus on mitochondria is motivated in part by their role in the energy metabolic regulation of dendritic spine activity. The dendritic spines are important sites of interactions among amyloid-beta accumulation, phosphorylated tau protein aggregates, excitatory glutamatergic neurotransmission, monoaminergic neuromodulation, depolarization, brain energy metabolism, and calcium homeostasis. In continuing tests, the MNA Unit collaborators now claim that mitochondrial mechanisms supporting dendritic spine activity, on the average, undergo improvement when they are appropriately challenged by respiratory stimuli, followed by periods of recovery. This is a process of survival of the fittest in which the challenges induce selective adaptive improvements of the work of those mitochondria that survive the challenges, with a resulting significant increase in the quality of mitochondrial function. Additionally, the collaborators argue that this type of stress-induced adaptation is particularly important in support of healthy aging, as proposed in a recent paper (Rodell et. al 2013).

Until recently, most work on mitochondrial involvement in aging and neurodegenerative diseases took place in vitro, with molecular imaging of cell cultures, experiments on isolated mitochondria, or studies of the genetics of DNA changes and protein expression. Considerable insight has emerged from this work but there is a striking lack of complementary evidence from processes studied in vivo, for example by means of methods of measuring mitochondrial variables affected by aging and contributing to age-related diseases.

The benefits that brain energy metabolism derives from blood flow regulation coupled to glucose delivery also are an issue. Glucose delivery is diffusion-limited rather than flow-limited, with a net extraction of about 10%, compared to oxygen delivery which is flow-limited with a net extraction of 40%: Thus glucose metabolism is not threatened by low blood flow because of very modest changes of extraction during functional activation, and glucose metabolism will not benefit significantly from flow increases. Therefore, we are now excited by emerging evidence that the reverse may be the case: It is not glucose consumption that benefits from increased blood flow, but blood flow regulation that benefits from increased glucose consumption. We claim that it is likely that it is the increased glucose consumption that indirectly drives the increased blood flow as a function of the degree of depolarization, which in turn drives both NO and lactate generations at or in vicinity of the post-synaptic density of dendritic spines. Reduced depolarization as a function of reduced signaling in neurodegeneration is then likely to reduce the drive on blood flow. The ability of mitochondria eventually to respond to depolarization of post-synaptic densities affects this relationship because of the involvement of lactate generation, but it also affects the health of mitochondria themselves, according to the hypothesis presented below, the testing of which is the main task of Anders Rodell and Michael Gejl in Brisbane.

In neurons, post-synaptic NMDA (N-methyl-D-aspartate) receptor activation induces both Ca2+ and cAMP increases that promote TORC (“transducer of regulated CREB”) import into the nucleus where it is involved in the transcription via the CREB (“cAMP response-element binding”) protein. Both TORC and CREB nuclear transcriptions have been shown to be potent activators of mitochondrial biogenesis. Thus, there is a strong need to correlate the in vitro evidence with data obtained in vivo. We propose to contribute to the data acquisition by testing the hypothesis that “intermittent challenges to the energy metabolism served by mitochondrial respiration with interspersed recovery (punctuated equilibria) maximize respiratory capacity and promote healthier and more numerous mitochondria. “ This is a genuine case of in vitro evidence in search of in vivo testing.

The testing of the hypothesis suffers from a lack of in vivo approaches to the study of mitochondrial function and dysfunction in vivo. Further progress requires correlation of different in vivo methods at different resolution scales with the evidence obtained in vitro. In turn, variables obtained in vitro then serve to qualify and quantify the data obtained in vivo. In order to measure the in vivo efficiency of the different metabolic pathways and the functional capacity of mitochondria, it is essential to measure not only the respiratory function in vivo,  but also the number of mitochondria and respiratory electron transfer chains, as well as the energy produced by different pathways.

Future studies of mitochondrial efficiency in neurodegeneration must address 1) how divergent metabolic pathways subserve and optimize metabolism (aerobic glycolysis in relation to oxidative phosphorylation), 2) how much of energy substrate turnover (measured as oxygen and glucose consumption, and fatty acid metabolism) relates to which magnitudes of the membrane potential of mitochondria (measured with [18F]triphenyl-phosphonium, for example) and proton flow, and 3) how many electron transfer chain complexes or entire mitochondria that actually relate to rates of energy turnover in response to each challenge. It is at present impossible to measure the number of electron transfer chains relative to the number of mitochondria in vivo, in part because labeling of the complexes cannot easily be distinguished from stains of other components such as red blood cells.

Publications of the NMA Unit in 2013: 

  1. Alstrup AK, Landau AM, Holden JE, Jakobsen S, Schacht AC, Audrain H, Wegener G, Hansen AK, Gjedde A, Doudet DJ. Effects of anesthesia and species on the uptake or binding of radioligands in vivo in the Göttingen minipig. Biomed Res Int. 2013;2013:808713. doi: 10.1155/2013/808713. Epub 2013 Sep 8. PubMed PMID: 24083242; PubMed Central PMCID: PMC3780537.
  2. Bailey CJ, Sanganahalli BG, Herman P, Blumenfeld H, Gjedde A, Hyder F (2012) Analysis of Time and Space Invariance of BOLD Responses in the Rat Visual System. Cereb Cortex. 2013 Jan;23(1):210-22. doi: 10.1093/cercor/bhs008. Epub 2012 Jan 31. PubMed PMID: 22298731; PubMed Central PMCID: PMC3513959. 
  3. Callesen MB, Hansen KV, Gjedde A, Linnet J, Møller A. Dopaminergic and clinical correlates of pathological gambling in Parkinson's disease: a case report. Front Behav Neurosci. 2013 Jul 29;7:95. doi: 10.3389/fnbeh.2013.00095. eCollection 2013. PubMed PMID: 23908610; PubMed Central PMCID: PMC3725950. 
  4. Darusman HS, Call J, Sajuthi D, Schapiro SJ, Gjedde A, Kalliokoski O, Hau J. Delayed response task performance as a function of age in cynomolgus monkeys (Macaca fascicularis). Primates. 2013 Nov 19. [Epub ahead of print] 
  5. Darusman HS, Sajuthi D, Kalliokoski O, Jacobsen KR, Call J, Schapiro SJ, Gjedde A, Abelson KS, Hau J. Correlations between serum levels of beta amyloid, cerebrospinal levels of tau and phospho tau, and delayed response tasks in young and aged cynomolgus monkeys (Macaca fascicularis). J Med Primatol. 2013 Jun;42(3):137-46. doi: 10.1111/jmp.12044. Epub 2013 Mar 26. 
  6. Fast R, Rodell A, Gjedde A, Mouridsen K, Alstrup AK, Bjarkam CR, West MJ, Berendt M, Møller A. PiB Fails to Map Amyloid Deposits in Cerebral Cortex of Aged Dogs with Canine Cognitive Dysfunction. Front Aging Neurosci. 2013 Dec 30;5:99. doi: 10.3389/fnagi.2013.00099. eCollection 2013. 
  7. Gejl M, Lerche S, Egefjord L, Brock B, Møller N, Vang K, Rodell AB, Bibby BM, Holst JJ, Rungby J, Gjedde A. Glucagon-like peptide-1 (GLP-1) raises blood-brain glucose transfer capacity and hexokinase activity in human brain. Front Neuroenergetics. 2013;5:2. doi: 10.3389/fnene.2013.00002. Epub 2013 Mar 27. PubMed PMID: 23543638; PubMed Central PMCID: PMC3608902. 
  8. Gejl M, Lerche S, Mengel A, Møller N, Bibby BM, Smidt K, Brock B, Søndergaard H, Bøtker HE, Gjedde A, Holst JJ, Hansen SB, Rungby J. Influence of GLP-1 on Myocardial Glucose Metabolism in Healthy Men during Normo- or Hypoglycemia. PLoS One. 2014 Jan 6;9(1):e83758. doi: 10.1371/journal.pone.0083758. PubMed PMID: 24400077; PubMed Central PMCID: PMC3882300. 
  9. Gjedde A, Aanerud J, Braendgaard H, Rodell AB. Blood-brain transfer of Pittsburgh compound B in humans. Front Aging Neurosci. 2013 Nov 7;5:70. doi: 10.3389/fnagi.2013.00070. eCollection 2013. 
  10. Ioannides AA, Liu L, Poghosyan V, Saridis GA, Gjedde A, Ptito M, Kupers R. MEG reveals a fast pathway from somatosensory cortex to occipital areas via posterior parietal cortex in a blind subject. Front Hum Neurosci. 2013 Aug 5;7:429. doi: 10.3389/fnhum.2013.00429. eCollection 2013. PubMed PMID: 23935576; PubMed Central PMCID: PMC3733019. 
  11. Kumakura Y, Gjedde A, Caprioli D, Kienast T, Beck A, Plotkin M, Schlagenhauf F, Vernaleken I, Gründer G, Bartenstein P, Heinz A, Cumming P. Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients. PLoS One. 2013 Sep 11;8(9):e73903. doi: 10.1371/journal.pone.0073903. eCollection 2013. 
  12. Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, Lauritzen F, Attramadal H, Storm-Mathisen J, Gjedde A, Bergersen LH. Lactate Receptor Sites Link Neurotransmission, Neurovascular Coupling, and Brain Energy Metabolism. Cereb Cortex. 2013 May 21. [Epub ahead of print] 
  13. Medin T, Rinholm JE, Owe SG, Sagvolden T, Gjedde A, Storm-Mathisen J, Bergersen LH. Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD). Neuroscience. 2013 Jul 9;242:11-20. doi: 10.1016/j.neuroscience.2013.03.036. Epub 2013 Mar 27. PubMed PMID: 23541742. 
  14. Petersen B, Gjedde A, Wallentin M, Vuust P. Cortical plasticity after cochlear implantation. Neural Plast. 2013; 2013: 318521. doi: 10.1155/2013/318521. Epub 2013 Nov 26. PubMed PMID: 24377050; PubMed Central PMCID: PMC3860139. 
  15. Rodell A, Aanerud J, Braendgaard H, Gjedde A. Washout allometric reference method (WARM) for parametric analysis of [11C]PIB in human brains. Front Aging Neurosci. 2013 Nov 27;5:45. doi: 10.3389/fnagi.2013.00045. eCollection 2013. 
  16. Rodell A, Rasmussen LJ, Bergersen LH, Singh KK, Gjedde A. Natural selection of mitochondria during somatic lifetime promotes healthy aging. Front Neuroenergetics. 2013 Aug 12;5:7. doi: 0.3389/fnene.2013.00007. eCollection 2013. 
  17. Stankowska AUM, Gjedde A. Perspective: Food addiction, caloric restriction, and dopaminergic neurotransmission. Acta Neuropsychiatr. 2013;:1. DOI: http://dx.doi.org/10.1017/neu.2013.18

Detailed description of the MNA Unit

Introduction
Background and Strategy
Objective
Hypotheses
Specific Aims
Benefits to Society
Benefits to Researchers
Methods
Participants, Organization and Management
National and International Partners 

Introduction

The size of the elderly population and the number of individuals afflicted by aging-related cognitive dysfunction is increasing rapidly in many developed countries. It has been estimated that by the year 2030, approximately 20% of the population over the age of 65 in Nordic countries and other developed countries will develop symptoms of neurocognitive dysfunction such as Alzheimer's disease (AD), mild cognitive impairment (MCI) and subjective cognitive impairment (SCI). Care of these individuals has large social and financial costs and represents a large burden to patients, families and the medical system. Thus, improved diagnostic, preventive and therapeutic tools are needed to manage this population and their needs. Improved understanding of the causes and mechanisms of neurodegeneration associated with these diseases is important to foster and facilitate such progress and reduce the anticipated burden of this health crisis in the 21st century.

Background and StrategyTil toppen

To address the impending medical and social challenges associated with the neurodegeneration in a population of increasing longevity, and to fulfil the critical research needs of healthy aging, we have over a period of some years built a strategic research theme focused on the molecular neurobiology of aging (MNA) with a view to the importance of raising the number of individuals who proceed to enjoy healthy aging of the brain. The MNA theme is pursued within the extensions of a strong interdisciplinary environment with essential and complementary expertise in neurosciences, psychology, molecular biology, molecular genetics, physiology, and high-resolution neuroimaging. The theme is supported by an alliance of associated research groups in three Nordic countries as well as in the United States and includes one biotech company in the context of brain energy metabolism.

The active research has the main aim of elucidation of the neurobiological differences between the energy metabolic processes of healthy and unhealthy aging, and hence of the pathogenesis and progression of Minor Cognitive Impairment (MCI) and Alzheimer’s disease (AD), analyzing the role of mitochondrial function and mitochondrial genome stability in these disorders, as well as to identify biomarkers for susceptibility and potential treatment of the diseases.

ObjectiveTil toppen

The objective of the thematic approach is to test the claim that the molecular neurobiology of aging underlies the differences between healthy and unhealthy aging of the brain. We seek to meet the objective by means of combined neurogenetics and neuroenergetics approaches to brain aging in the manifestation of mild cognitive impairment on one hand and Alzheimer’s disease on the other. Clearly, the early etiologies of MCI and AD are poorly understood, but they are held to involve environmental, epigenetic, and genetic factors. The AD incidence increases exponentially with age, and current evidence suggests that oxidative stress is intimately associated with the pathophysiology of AD. The evidence points to a key role for mitochondrial abnormalities in AD, and DNA repair defects have been associated with AD, early aging disorders (progerias), and neurodegenerative diseases (West 2007). Thus, brains from individuals with AD or MCI recently revealed evidence of defective base excision repair (BER) (Weissman et al 2008).

HypothesesTil toppen

The research associated with the theme is centred on three fundamental hypotheses, each of which relates to findings of substantial variation in the overall energy consumption measured in the brains of different individuals who do not otherwise differ significantly with respect to cognition (Gjedde et al. 2010):

  1. Partial uncoupling of mitochondrial function and the resulting differences in individual energy production result in significant inter-individual differences in RONS (reactive oxygen and nitrogen species) generation, protein damage, and repair activity, and these differences contribute directly to variations of aging health.
  2. There are significant correlations between inter-individual differences of brain energy metabolism, brain morphology, and functional brain activity.
  3. There is a direct relationship between energy turnover in the brain and the aging process that can be established by aligning population-based observations of aging processes with measures associated with brain energy metabolism and mitochondrial function.

Specific AimsTil toppen

The efforts under this theme are designed to establish the pathogenesis and progression of MCI and AD, and to identify biomarkers for susceptibility and potential treatment of these diseases. For this purpose, cognitive, clinical, mitochondrial activity, and DNA repair profiles continuously are assessed in cohorts of MCI and AD-afflicted individuals, and in comparable cohorts of healthy volunteers. The results significantly impact on the understanding and management of aging-related human diseases, including neurodegeneration and brain malignancies.

Because neurons generally do not replicate (with important exceptions in the hippocampus and the entorhinal cortex at certain ages), mechanisms that contribute to the survival of neurons are particularly important to the salvation of the particular brain functions that depend on these neurons. DNA oxidation and repair defects are known to occur in patients with AD or MCI. On the basis of these findings, we systematically evaluate the associations between mitochondrial function, DNA repair profiles, and cognitive decline in separate cohorts of MCI and AD patients, and in comparable individuals with normal cognitive function. These studies specifically address a triad of issues, consisting of the questions, do 1) oxidative DNA damage, 2) defective repair, or 3) mitochondrial dysfunction contribute separately or in combination to cognitive decline and to the progression of MCI and AD? The answers predictably provide a basis for improved AD diagnosis and management.

Mitochondria play a unique role in cellular homeostasis. Mitochondrial oxidative phosphorylation generates endogenous reactive oxygen and nitrogen species (RONS), which have the potential to damage DNA, proteins, and lipids. When RONS attack DNA, the resulting damage includes oxidized bases and strand breaks. Because neurons have a high rate of oxygen consumption and low levels of antioxidants, the investigations that we complete proceed under the assumption that neurons are more susceptible than other cell types to RONS-induced oxidative damage. This claim is consistent with the observation that mtDNA damage and mitochondrial dysfunction play a role in age-associated neurodegenerative disorders.

The current understanding holds that mtDNA has eluded the evolutionary relocation of DNA to the nucleus of the cell because mtDNA is essential to the regulation of oxidative metabolism in single, individual mitochondria. Specific mtDNA repair importantly protects the comparatively more fragile mitochondrial genome against RONS-induced mtDNA damage. When the repair mechanisms fail or are overwhelmed, apoptosis sets in to rid the cell of individually malfunctioning mitochondria, and ultimately of whole neurons holding the malfunctioning mitochondria.

The thematic efforts of the researchers that belong to the unit are designed to explore each link of this chain, i.e., to establish whether correlations exist between mtDNA repair capacity, mitochondrial dysfunction, and age-related diseases reflecting failures of the repair mechanism leading to failure of brain energy metabolism and apoptotic loss of connectivity and cells.

Benefits to SocietyTil toppen

It is commonly recognized that brain researchers will identify many of the fundamental principles of neural operation within the next decades. Increased resources to neuroscience thus are expected to lead to treatments of some of the most devastating, prevalent, and costly neurological and neuropsychiatric disorders. The MNA unit exists to meet the multidisciplinary challenges of reaching this goals. The unit focuses on the characterization of the nature and source of oxidative DNA damage in the brain and the consequences for brain energy metabolism in normal aging and in MCI and AD patients. The characterization substantially adds to current findings and tests current hypotheses of the association between oxidative stress and the pathogenesis of AD in pathogenesis, and identifies the therapeutic possibilities that greater insight into DNA repair and mitochondrial targets offers for the prevention and treatment of this disease.

In the next decades, the aging of the post-war baby boom in western societies inevitably will lead to a corresponding boom of aged citizens with wide ranging clinical and social implications. Considering the expanding numbers of elderly in society, studies of health and disease in the elderly increasingly is important. The number of cases with AD increases worldwide. There is a clear demand for improved understanding of the pathogenesis of AD for therapeutic reasons in the realm of public health. To meet this challenge, we seek to understand the molecular mechanisms of AD pathogenesis and other neurodegeneration, and the role of mitochondrial genome damage induced by oxidative stress in these processes.
AD runs a protracted course from the time of diagnosis and is detrimental also to the health of caregivers. In a system of managed care, AD also is a severe burden to the public health system; the economic impact is by some estimates already larger than that of cancer, stroke and heart disease. AD prevalence increases from 10% above 65 years of age, to 50% among those above 85 and may quadruple by 2050 due to incidence rates that increase exponentially with age and a larger number of elderly.

Research results are disseminated widely, including at international meetings and in high impact international journals, as well as educationally (centres, postgraduate courses, and publications). Results frequently are presented to the lay public and decision makers.

Benefits to ResearchersTil toppen

The MNA unit enables the characterization of the nature and source of oxidative nucleic acid damage in MCI and AD patents versus healthy controls in Scandinavia. This substantially has added to current facts and hypotheses on the association between oxidative stress and AD in pathogenesis, as well as to the therapeutic possibilities that mitochondrial DNA repair targets might offer for the prevention and treatment of this disease. Specifically, researchers benefit from:

  1. The combined efforts of the MNA thematic efforts in building Nordic cohorts of healthy volunteers and patient groups is a unique opportunity to create materials of critical mass for statistics and also for subsequent meta-analyses.
  2. Contributions to biobanks: The biological material collected in the course of these investigations is stored and made available to researchers everywhere.
  3. The search for biomarkers for MCI and AD in blood and CSF gives rise to improved diagnostics and monitoring of progression as well as to intensified industrial spin-offs.
  4. Training of students and scientists in clinical and molecular neuroscience and imaging, through combinations of laboratory exchange, website-based self-tutorials and practical courses, ensures improved scientific progress and interactions.

MethodsTil toppen

Pathophysiological, cognitive, clinical, and DNA repair profiles are assessed in cohorts of MCI and AD-afflicted individuals:

  1. Comparisons of oxygen consumption, brain energy metabolism (ATP turnover), and cerebral blood flow using PET, fMRI and MRS technology are compared in healthy volunteers aged 20-80 years and age-matched groups of patients with MCI, AD or Parkinson’s disease.
  2. Mitochondrial function using Seahorse technology and DNA repair profiles is assessed in cohorts of healthy volunteers 20-75 years of age.
  3. Mitochondria from brain regions of interest in aging mice are isolated by laser dissection microscopy, and the incidence of point mutations is determined. This work provides important insights into the sequence and potential mechanistic interactions of the age-dependent processes. We use high throughput sequencing of mitochondrial DNA to analyze mitochondrial mutations, mitochondrial polymorphisms, examine mitochondrial deletions at the single cell level, and estimate mitochondrial mutation rates. 

Participants, Organization and ManagementTil toppen

The researchers of the unit are uniquely qualified to maintain international excellence within the MNA theme:

  1. Researchers and affiliates of the MNA unit have a strong and unique presence in molecular genetics and mitochondrial biology in the context of MCI and AD pathogenesis.
  2. Researchers and affiliates of the MNA unit have strong competence in functional and pathophysiological brain imaging.
  3. Clinical materials from healthy volunteers, MCI and AD patients and transgenic mice models are available to MNA researchers and affiliates.
  4. The MNA unit is affiliated with strong groups from basic research, psychology and clinical medicine that have good track records in multidisciplinary research.
  5. The MNA unit has access to advanced expertise in both clinical assessments (neurology and psychology) as well as in functional genomics, mitochondrial biology, and molecular biology. The results obtained by members of the MNA unit have a substantial added value in translational research because of the involvement of a commercial enterprise.
  6. The MNA unit brings together strong research groups with complementary expertise on molecular biology and genetics, cognitive genetics and comprehensive aspects of Alzheimer disease.

In short, advanced technology within molecular and cellular biology, transgenics, cognitive sciences, brain imaging and AD research along with existing relevant biobanks are included in the efforts of the MNA unit. The various participants all have strong international collaborations and networks. The capabilities of the members of the unit and strong institutional, national and international networks should ensure that the excellence can be successfully maintained.

This interdisciplinary unit masters the necessary comprehensive logistics, and teams collaborating in the analyses are located in Denmark, Norway, Sweden, and the United States, with extensive international collaborations.

Management of the unit is the responsibility of the Coordinator (Albert Gjedde, Department of Neuroscience and Pharmacology and Center for Healthy Aging, both University of Copenhagen). A project Management Office with ample experience in financial, administrative and project coordination assists the coordinator.

National and International Partners Til toppen

Denmark

Department of Neuroscience and Pharmacology, University of Copenhagen
Professor Albert Gjedde, MD DSc FRSC, Head of Department, email
Associate Professor Ron Kupers, PhD, email
Senior Research Associate Manoucher Vafaee, PhD, email
Postdoctoral Fellow Karen Johanne Pallesen, PhD, email
Graduate student Johan Stender, MD, email

Centre for Healthy Aging, University of Copenhagen
Professor Lene Juel Rasmussen, Director, Centre for Healthy Aging, email
Professor Albert Gjedde, email
Professor Ian D. Hickson, email
Professor Flemming Dela, email
Professor Niels Tommerup, email
Associate Professor Erik Lykke Mortensen, email
Aarhus University, 8000 Aarhus, Denmark
Associate Professor Tinna Stevnsner, email
Senior Research Associate Anders Rodell, PhD, email
Graduate student Adjmal Nahimi, email
Graduate student Joel Aanerud, MD, email
Graduate student Christopher Bailey, MSc, email
Seahorse Bioscience Europe, Copenhagen, Denmark
Dr. Per Bo Jensen, email

United States

National Institute of Aging, NIH, Baltimore, USA
Professor Vilhelm A. Bohr, Director, email


Norway

Centre for Molecular Biology and Neuroscience (CMBN), University of Oslo, NO-0317 Oslo, Norway
Professor Tone Tønjum, CMBN Director and ABH head, email
Professor Jon Storm-Mathisen, CMBN Co-director, email
Associate Professor Linda Bergersen, email


Sweden

Department of Neuropsychiatry, Sahlgrenska Universitetssjukhuset, SE-431 41 Mölndal, Sweden
Professor Anders Wallin, email