Albert Gjedde

University of Copenhagen · Department of Neuroscience

Alzheimer’s disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. The canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the...

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid‐β hypothesis, while significant, has faced setbacks, highlighting t...

Dr. Sean Marrett, a treasured neuroscientist and highly engaged member of the international brain mapping community for more than three decades, passed away on December 12, 2023 after a 16 month battle with Mesothelioma. His impact went beyond scientific productivity. He was a friend, colleage, and inspiration to perhaps thousands across discipline...

We investigated the feasibility of using a dopamine transporter (DaT) tracer ligand ([¹²³I]FP-CIT) along with novel multi-pinhole brain collimators for dynamic brain single photon emission computed tomography (SPECT) in suspected Parkinson's disease patients. Thirteen patients underwent dynamic tracer acquisitions before standard imaging. Uptake va...

: Introduction: Increased theta and delta power and decreased alpha and beta power, measured with quantitative electroencephalography (EEG), have been demonstrated to have utility for predicting the development of dementia in patients with Parkinson’s disease (PD). Noradrenaline modulates cortical activity and optimizes cognitive processes. We clai...

Background: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD). Elevated periosteal pressure sensitivity (PPS) at the sternum relates to ANSD and sympathetic hyperactivity. Two previous observational case–control studies of the effect of reduction of PPS suggested lower all-cause mortal...

Introduction Depression in ischemic heart disease (IHD) is associated with increased mortality, and autonomic nervous system dysfunction (ANSD) may link the two conditions. Regulatory functions of the autonomic nervous system with respect to IHD risk factors include heart rate, blood pressure, serum cholesterol, and glycated hemoglobin. While painf...

Objective: We investigated the association between peripheral insulin resistance (IR) and brain glucose uptake (BGU) and further determined if testing condition (fasting vs. hyperinsulinemic-euglycemic clamp) was a moderator of the association. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science, studi...

Background The autonomic nervous system (ANS) maintains glucose homeostasis. While higher than normal glucose levels stimulate the ANS toward reduction, previous findings suggest an association between sensitivity to, or pain from, pressure at the chest bone (pressure or pain sensitivity, PPS) and activity of the ANS. A recent randomized controlled...

Introduction: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD) and has been found also to be related to elevated measures of sensitivity to pain from pressure (PPS) at the sternum. Previously, we found that non-pharmacological intervention by peripheral sensory nerve stimulation, moni...

Objective: Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a...

The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the...

Values of binding potentials (BPND) of dopamine D2/3 receptors differ in different regions of the brain, but we do not know with certainty how much of this difference is due either to different receptor numbers, or to different affinities of tracers to the receptors, or to both. We tested the claim that both striatal and extrastriatal dopamine D2/3...

Long-term alteration of dopaminergic neurotransmission is known to modulate the D2/D3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [11C] raclopride. To obtain accurate measurem...

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve...

Background: Values of binding potentials (BPND) of dopamine D2/3 receptors differ in different regions of the brain, but we do not know with certainty how much of this difference is due either to different receptor numbers, or to different affinities of tracers to the receptors, or to both. Method: We tested the claim that both striatal and extrast...

The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the...

Hypothesis and predictions: Here, we claim that amyloid beta (Aβ) accumulation is a protective mechanism that ultimately fails. We predict that more Aβ accumulates in regions with higher rates of glucose metabolism, reaching a maximum followed by progression of pathology. Background: Aβ accumulation is characteristic of Alzheimer's disease (AD)...

The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the...

Background Disturbances in presynaptic dopamine activity and levels of gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsych...

In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is...

Background Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of ¹⁸F-DOPA to ¹⁸F-dopamine (k3) and the effect of treatment on psychotic symptoms in antipsychotic-naïve first-episode psychotic patients. We further...

Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting...

We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis...

We derived three widely used linearizations from the definition of receptor availability in molecular imaging with Positron Emission Tomography. The purpose of the present research was to determine the convergence of the results of the three methods in terms of three parameters, occupancy (s), distribution volume of the non-displaceable binding com...

Quantitative measurements of resting cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO 2 ) show large between-subject and regional variability, but the relationships between CBF and CMRO 2 measurements regionally and globally are not fully established. Here, we investigated the between-subject and regional associations between CBF and CM...

Objective: By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults b...

Background Autonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism in the mammalian body. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects this convention. Objectives The present study tested the role of cerebral regulation of ANSD a...

RationaleAfter alcohol ingestion, the brain partly switches from consumption of glucose to consumption of the alcohol metabolite acetate. In heavy drinkers, the switch persists after abrupt abstinence, leading to the hypothesis that the resting brain may be “starved” when acetate levels suddenly drop during abstinence, despite normal blood glucose,...

Background: Muscarinic acetylcholine receptor 4 (M4) modulates dopaminergic neurotransmission and is a target for novel treatments of schizophrenia, cognitive deficits, and addiction. Impulsive and compulsive behaviors are key traits of addiction, yet the importance of M4 receptor signaling to these traits is poorly understood. We investigated impu...

Objective: We report the transcranial functional photoacoustic (fPA) neuroimaging of N-methyl-D-aspartate (NMDA) evoked neural activity in the rat hippocampus. Concurrent quantitative electroencephalography (qEEG) and microdialysis were used to record real-time circuit dynamics and excitatory neurotransmitter concentrations, respectively. Approac...

Purpose Anaesthesia routinely is used in animal neuroimaging in order to reduce head motion artefacts and minimize the influence of stress. However, anaesthetics can modify radioligand binding profiles at receptor targets studied by positron emission tomography (PET). Here, we determined the effects of two routine anaesthetics on the binding of a t...

Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (μ-opioid receptor agonist) and [11C]rac...

Transcranial functional photoacoustic (fPA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of current neuroimaging modalities. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial fPA neuroim...

According to the World Health Organization (WHO), dementia is a disorder that occurs as result of a neurodegenerative process in brain, and usually is chronic or progressive by nature. Most descriptions of senile dementia date back to Alois Alzheimer. In 1906, Alzheimer described the first patient, Auguste Deter, who suffered from the disorder that...

Minimally-invasive monitoring of electrophysiological neural activities in real-time—that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET—presents a very challenging yet significant task for neuroimaging. In this paper, we present in vivo functional PA (fPA) imaging of...

The glymphatic system is a brainwide CSF transport system that uses the perivascular space for fast inflow of CSF. Arterial pulsations are a major driver of glymphatic CSF inflow, and hypertension that causes vascular pathologies, such as arterial stiffening and perivascular alterations, may impede the inflow. We used dynamic contrast-enhanced MRI...

Purpose We tested the hypothesis that lateralized hemispheric glucose metabolism may have diagnostic implications in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Methods We performed FDG-PET/CT in 23 patients (mean age 63.7 years, range 50–78, 17 females) diagnosed with AD (n = 15) or MCI (n = 8) during a six-month period in 2014....

Background: Electroconvulsive therapy is an effective therapy of depression. We hypothesized that the beneficial effects are mediated partly by decreased serotonin receptor availability in the cortex. Aims: We used positron emission tomography with the serotonin 5HT2A receptor radioligand [11C]MDL100,907 to determine serotonin receptor availabil...

Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10), administration are known to stimulate mitochondrial electron...

Background: The alleged procognitive effects of nicotine and its metabolites in brain are controversial. Objective: Here, we review the pharmacologically active metabolites of nicotine in brain and their effects on neuronal mechanisms involving two main cognitive domains, i.e., learning and memory. Methods: We searched Embase, Medline via PubMed, S...

INTRODUCTION: Stress is one of the greatest burdens of our society and often implies impairments in cognitive and emotional functions. Here, we hypothesise that changes in the brain's dopamine (DA)-based mesocorticolimbic projec-tions in patients with work-related stress (adjustment disorder) will manifest themselves as altered glucose metabolism i...

Brain growth across childhood is a dynamic process associated with specific energy requirements. A disproportionately higher rate of glucose utilization (CMRglucose) compared with oxygen consumption (CMRO2) was documented in children's brain and suggestive of non-oxidative metabolism of glucose. Several candidate metabolic pathways may explain the...

Purpose: Malignant cells exhibit increased rates of aerobic glycolysis. Here, we tested whether the accumulation of fluoro-deoxyglucose-6-phosphate (FDG6P) in ovarian cancers of differential malignancy reflects inversely correlated elevations of hexokinase (HK) and glucose-6-phosphatase (G6Pase) activities. Procedures: Twenty-nine women with sus...

Here, we tested the claim that nicotine attenuates the signs of brain dysfunction in the model of brain aging induced by D-galactose (DGal) in mice. We administered nicotine at doses of 0.1, 0.5 and 1 mg/kg by the subcutaneous (s.c.) or at 0.1 mg/kg by the intranasal (i.n.) routes in mice that had received DGal at the dose of 500 mg/kg subcutaneous...

Because the human brain consumes a disproportionate fraction of the resting body’s energy, positron emission tomography (PET) measurements of absolute glucose metabolism (CMR glc ) can serve as disease biomarkers. Global mean normalization (GMN) of PET data reveals disease-based differences from healthy individuals as fractional changes across regi...

Figure S1: voxel-to-voxel correlations of qCMRglc in gray matter of the human brain. Figure S2: voxel-to-voxel correlations of qCMRglc in white matter of the human brain. Figure S3: thresholded t-maps of metabolic variations in disorders of consciousness. Figure S4: thresholded t-maps of metabolic variations in anesthetic sedation. Figure S5: thres...

Transcranial photoacoustic (PA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of functional neuroimaging. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial PA with VSD (IR780) imaging in...

In the present study we tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1R and D2R density was...

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Background: The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7-nAChR suggests a role in cognition. Methods: We expanded the first-in-human PET imaging of α7-nAChR with [18F]ASEM from five to 21 healthy non-sm...

Aims/hypothesis: The aim of this randomised, crossover trial was to compare cognitive functioning and associated brain activation patterns during hypoglycaemia (plasma glucose [PG] just below 3.1 mmol/l) and euglycaemia in individuals with type 1 diabetes mellitus. Methods: In this patient-blinded, crossover study, 26 participants with type 1 di...

Referring to a recent international article stating that amyloid PET has a high additive value in making a diagnosis of Alzheimer's disease (AD) when previous investigations are inconclusive, the authors of this editorial argue that this statement is based on circular reasoning and, hence, misleading. Since autopsy findings and other potential indi...

The α7 nicotinic acetylcholine receptor (nAChR) increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The a7-nAChR primarily is located in cerebral cortex and sub-cortical regions, compared to the α4β2 nAChR subtype that has a more subcortical distribution. The highly cortical distribution suggests a...

Noradrenergic neurons in both the peripheral nervous system and in the central nervous system (CNS) undergo severe degeneration in patients with Parkinson's disease (PD). This loss of noradrenaline may play essential roles in the occurrence of a wide range of prevalent non-motor symptoms and can further complicate the lives of PD patients. In vivo...

There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1...

Incretin hormones, notably glucagon-like peptide-1 (GLP-1), are gluco-regulatory hormones with pleiotropic effects also in the central nervous system. Apart from a local production of GLP-1, systemic administration of the hormone has been shown to influence a number of cerebral pathologies, including neuroinflammation. Given the brains massive depe...

We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [¹¹C]yohimbine binding in brain to quantify the density and affinity of α2 adrenoceptors under condition of changing radioligand binding...

In this chapter, we review how light affects humans: first by describing the ways in which light impacts physiology and behavior, and then by discussing how different char- acteristics of light (timing, pattern, intensity, duration, and past light exposure) can influence alertness, cognitive performance, mood, sleep, and well-being, in addition to...

In this chapter, we review how light affects humans: first by describing the ways in which light impacts physiology and behavior, and then by discussing how different char- acteristics of light (timing, pattern, intensity, duration, and past light exposure) can influence alertness, cognitive performance, mood, sleep, and well-being, in addition to...

Minimally-invasive monitoring of electrophysiological neural activities in real-time—that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET—presents a very challenging yet significant task for neuroimaging. In this paper, we present in vivo functional PA (fPA) imaging of...

Rationale: Degeneration of noradrenergic neurons may underlie the disabling non-motor symptoms in patients with Parkinson's disease. Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand (11)C-MeNER is a highly...

Leber's Hereditary Optic Neuropathy (LHON) shares features with Multiple Sclerosis (MS). Both diseases develop optic lesions. Frequent secondary LHON mutations in MS patients may explain the optic damage. Here, we tested the hypothesis that secondary LHON mutations are associated with optic neuritis (ON) in MS patients. We recruited 56 MS subjects...

Evidence suggests that synapses are affected first in Parkinson’s disease (PD). Here, we tested the claim that pathological accumulation of α-synuclein, and subsequent synaptic disruption, occur in absence of dopaminergic neuron loss in PD. We determined early synaptic changes in rats that overexpress human α-synuclein by local injection of viral-v...

Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Götting...

Ischaemic heart disease and stroke are vascular events with serious health consequences worldwide. Recent genetic and epigenetic techniques have revealed many genetic determinants of these vascular events and simplified the approaches to research focused on ischaemic heart disease and stroke. The pathogenetic mechanisms of ischaemic heart disease a...

Background: Multiple sclerosis (MS) is considered a pathogenetic enigma. Recently, efforts to implicate genetics in human susceptibility to MS have identified an important role of mitochondrial DNA (mtDNA). G13708A is a common mtDNA variation associated with MS in specific populations. This study tested the hypothesis that the mtDNA G13708A variat...

Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [¹¹C]Pittsburgh Compound B ([¹¹C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer’s disease, and healthy volunteers. The method...

Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegenera...

Purpose: Diaschisis denotes brain dysfunction remote from a focal brain lesion. We have quantified diaschisis and investigated its prognostic value in glioma. Methods and material: We compared 50 (18)F-FDG-PET-CT studies collected prospectively from 14 patients with supratentorial glioma (5 men and 9 women aged 35-77 years) with 10 single scans...

Brain energy metabolism is held to reflect energy demanding processes in neuropil related to the density and activity of synapses. There is recent evidence that men have higher density of synapses in temporal cortex than women. One consequence of these differences would be different rates of cortical energy turnover and blood flow in men and women....

In retina, like in brain, lactate equilibrates across cell membranes via monocarboxylate transporters and in the extracellular space by diffusion, forming a basis for the action of lactate as a transmitter of metabolic signals. In the present paper, we argue that the lactate receptor GPR81, also known as HCAR1, may contribute importantly to the con...

In animal models, the incretin hormone GLP-1 affects Alzheimer’s disease (AD). We hypothesized that treatment with GLP-1 or an analogue of GLP-1 would prevent accumulation of Aβ and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analogue liragluti...

Differentiation of the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS) is a persistent clinical challenge [1]. Based on positron emission tomography (PET) studies with [(18)F]-fluorodeoxyglucose (FDG) during sleep and anesthesia, the global cerebral metabolic rate of glucose has been proposed as an indicator of consc...