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- Brun, Arne
(author)
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Alzheimer´s and other neurodegenerative cognitive disorders. : A strategy to find cause and cure
- 2018
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In: Acta Scientiarum Lundensia. - 1651-5013. ; 2018:006, s. 1-11
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Journal article (peer-reviewed)abstract
- The aim of this treatise is to sketch out a strategy how to find a cause and cure for cognitive brain disorders and then primarily Alzheimer’s disease (AD) based on recent and little explored research progress. Step one is to find the cause. Recent evolution has supplied the human brain with new astrocytes which regarding their remarkable properties can be expected to harbor the cause of AD and several other cognitive neurodegenerative disorders. Plausible causes have already been proposed and will be accounted for in what follows. A cause proved or made plausible provides a good ground for finding a therapy. We must also be able to diagnose the disorder at an early stage ahead of widespread and severe brain damage for a treatment not to leave behind a crippling condition! This possibility appears now to become a reality since recent research has identified the same changes in the retina as in the brain. They can there be diagnosed with modern ophthalmological techniques and appear long before brain damage produces symptoms during the several decades long silent phase when AD is under way. After arrest of the disorder the neuronal plasticity can be expected to deliver repair, more the earlier the disorder is arrested.
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| 2. |
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| 3. |
- Brun, Arne
(author)
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Recent discoveries widen the basis for future research in Alzheimer´s disease.
- 2016
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In: Acta Scientiarum Lundensia. - 1651-5013. ; 2016:002, s. 1-12
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Research review (other academic/artistic)abstract
- Abstract. Intended as food for thought this revue offers a general orientation on Alzheimer’s disease (AD) with comments on the brain changes and clinical features. But more importantly, it points out recent research findings which may offer new alleys for AD research pertinent to the etiology and pathogenesis of AD and alternatives to the so far rather unfruitful and costly amyloid research trail. This new knowledge thus comes from various fields of research such as epigenetics, pointing to possible environmental etiologic factors. Further exosomes may provide information on the state of the neuronal population for diagnostic purposes and might become useful as carriers of therapeutic substances. The newly disclosed protein complexity of the synapses may harbor a large yet unexplored field for neurochemical research pertinent to the early or likely initial loss of synapses in Alzheimer disease. The finding of a more generalized neuronal gene disturbance in Alzheimer’s disease shifts the focus from age related changes to developmental disturbances and increased neuronal vulnerability. BBB incompetence with a start in the hippocampus has also recently been pointed out and may initiate the degenerative process of Alzheimer’s disease. Finally, recent basic research findings on glial evolution, underscoring the distance between humans and rodents, our prime disease model animal, points to several new unexplored mechanisms, which may be relevant for the understanding of neurodegenerative processes. Also stressed is the need to institute treatment at an early stage of the disease, necessitating research for markers, which will enable a diagnosis way ahead of the widespread damage present at the time of clinical debut.
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| 4. |
- Brun, Arne, et al.
(author)
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The Birth and Early Evolution of the Frontotemporal Dementia (FTD) Concept.
- 2011
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In: Journal of Molecular Neuroscience : MN. - : Springer Science and Business Media LLC. - 1559-1166 .- 0895-8696. ; 45, s. 324-329
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Journal article (peer-reviewed)abstract
- An historical overview of the development of the concept of frontotemporal dementia is presented, regarding the last 30 years, using as a backbone the conferences held on this theme, with a start in 1986 in Lund, Sweden. Since then, a dramatic increase in research activities and publications has rapidly expanded our knowledge in this field, a step necessary for the ultimate goal to find an effective treatment of this devastating disorder.
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| 5. |
- Gustafson, Lars, et al.
(author)
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A factor analytic approach to symptom patterns in dementia.
- 2010
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In: International Journal of Alzheimer's Disease. - : Hindawi Limited. - 2090-0252 .- 2090-8024.
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Journal article (peer-reviewed)abstract
- Previous publications have shown a high diagnostic sensitivity and specificity of three short clinical rating scales for Alzheimer's disease (AD), frontotemporal dementia (FTD), and vascular dementia (VaD) validated against neuropathological (NP) diagnoses. In this study, the aim was to perform an exploratory factor analysis of the items in these clinical rating scales. The study included 190 patients with postmortem diagnoses of AD (n = 74), VaD (n = 33), mixed AD/VaD (n = 31), or FTD (n = 52). The factor analysis produced three strong factors. Factor 1 contained items describing cerebrovascular disease, similar to the Hachinski Ischemic Score. Factor 2 enclosed major clinical characteristics of FTD, and factor 3 showed a striking similarity to the AD scale. A fourth symptom cluster was described by perception and expression of emotions. The factor analyses strongly support the construct validity of the diagnostic rating scales.
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| 6. |
- Gustafson, Lars, et al.
(author)
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The accuracy of short clinical rating scales in neuropathologically diagnosed dementia.
- 2010
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In: The American journal of geriatric psychiatry. - 1064-7481 .- 1545-7214. ; 18:9, s. 810-820
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Journal article (peer-reviewed)abstract
- Objective: The overall aim was to evaluate to what extent the diagnosis of dementia subtypes, obtained by three clinical rating scales, concurred with postmortem neuropathologic (NP) diagnosis of Alzheimer disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD) and mixed AD/VaD. Design: A prospective longitudinal clinical work-up with postmortem NP examination. Participants: Two hundred nine patients with dementia referred for clinical evaluation and follow-up. Methods: The diagnostic scores in a set of three short clinical rating scales for AD, FTD, and VaD were evaluated against NP diagnoses. Results: The sensitivity and specificity of the AD scale were 0.80 and 0.87, respectively, of the FTD scale 0.93 and 0.92, respectively, and of the Hachinski Ischemic Score (HIS, VaD diagnosis) 0.69 and 0.92, respectively. Cases with mixed AD/VaD generally presented a combination of high AD and ischemic scores. A preferred cutoff score of six was identified for both the AD and FTD scales. Conclusions: All three clinical rating scales showed a high sensitivity and specificity, in close agreement with final NP diagnosis-for the HIS a moderate sensitivity. These scales may thus be considered good diagnostic tools and are recommended for clinical and research center settings.
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| 7. |
- Nielsen, Henrietta, et al.
(author)
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NG2 cells, a new trail for Alzheimer's disease mechanisms?
- 2013
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In: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 1:1
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Journal article (peer-reviewed)abstract
- Neuron Glial 2 (NG2) cells are glial cells known to serve as oligodendrocyte progenitors as well as modulators of the neuronal network. Altered NG2 cell morphology and up-regulation as well as increased shedding of the proteoglycan NG2 expressed on the cell surface have been described in rodent models of brain injury. Here we describe alterations in the human NG2 cell population in response to pathological changes characteristic of Alzheimer's disease (AD).
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| 8. |
- Nittby, Henrietta, et al.
(author)
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Nonthermal GSM RF and ELF EMF effects upon rat BBB permeability
- 2011
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In: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 31:2, s. 140-148
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Journal article (peer-reviewed)abstract
- Since the late 1980s, our group has examined the effects of radiofrequency electromagnetic fields (RF-EMF), including pulse-modulated waves of the type emitted by mobile phones, upon the blood-brain barrier. In more than 2,000 rats, we have repeatedly demonstrated a passage of the rats' own albumin from the blood through the brain capillaries into the surrounding brain parenchyma at SAR values down to 0.1mW/kg. In most of these experiments, the animals were exposed in TEM-cells, ventilated by an external electrical fan at 50 Hz. In the present study, we examined whether the extremely low frequency (ELF) magnetic fields from the fan (50 Hz, 0.3-1.5 μT) might add to the RF effect. Sixty-four rats were divided into 4 groups: RF only, ELF only and RF + ELF exposure plus a sham group. The GSM-900 MHz RF exposure was at the very low, nonthermal, average whole-body SAR level 0.4 mW/kg. Demonstration of the normally occurring albumin extravasation in the basal hypothalamus is our inbuilt control proving that the staining is reliable. Two full series of staining of the whole material gave negative results for hypothalamus. Not until we changed to avidin, biotin, and antibodies from a third supplier, we received an acceptable staining. Twenty-five percent of the RF animals had a pathological albumin leakage, while the ELF and RF + ELF groups with three and two pathological findings, respectively, were not significantly different from the control group. We conclude that the use of external fans has had no major influence upon the result.
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| 9. |
- Persson, Bertil R, et al.
(author)
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Brain tumour growth in rats exposed to electromagnetic fields used in wireless cellular communication
- 2014
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In: Acta Scientiarum Lundensia. - 1651-5013. ; 2014:001, s. 1-23
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Journal article (peer-reviewed)abstract
- In 1996 there was no convincing laboratory evidence that EMFs used in wireless communication could cause tumour promotion at non-thermal exposure levels. Therefore we then performed a study of the effects from exposure to such electromagnetic fields in the rat brain glioma model we were using in our research for brain tumour therapy. By stereotaxic technique rat glioma cells (RG2 or N32) were injected into the head of the right caudate nucleus in 154 pairs of Fischer 344 rats in both exposed and matched controls. Starting on day 5 after inoculation, the animals were exposed for 7 hours a day, 5 days a week during 2 - 3 weeks. Rats of both sexes were exposed to electromagnetic fields in the microwaves frequency range 915 MHz both as continuous waves (1 W), and as pulse-modulated at 4, 8, 16 and 217 Hz in 0.57 ms long pulses and 50 Hz in 6.67 ms pulses, all with a maximum power amplitude of 2 W per pulse. The animals were kept un-anaesthetized in well-ventilated TEM cells during 7 hours a day for 5 days a week for 2-3 weeks. Their matched controls were kept in identical TEM cells without EMF exposure. At the end of the exposure period the rat brains were examined histopathologically. The tumour size was measured with a calliper and the volume estimated as an ellipsoid. Our study of the 154 matched pairs of rats did not show any significant difference in tumour volume between animals exposed to 915 MHz microwaves, and those not exposed. Thus our results did not support that daily exposure to EMF promotes tumour growth when given from the fifth day after the start of tumour growth in the rat brain until the sacrifice of the animal 16 days later. In the present review our results published 1997 have been re-evaluated in terms of SAR dependence of tumour volume observed ratio (exposed / control). We thus surprisingly found that the shape of tumour volume-OR versus SAR response was of bath-tube pattern, similar to that found in our parallel studies of albumin leakage through the blood-brain barrier. Since the SAR varies between most other animal studies reviewed and human epidemiological studies this SAR dependence might explain the controversy in rendering the results.
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| 10. |
- Persson, Bertil R, et al.
(author)
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Mörka Neuron och Mobiltelefoner : Dedicerad till en 90-årig man, Arne Brun i Lund
- 2021
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In: Acta Scientiarum Lundensia. - 1651-5013. ; 2021:001, s. 1-23
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Journal article (peer-reviewed)abstract
- Med denna svenska översikt av våra egna och andra forskares observationer av mörka neuron vid mikrovågs exponering från mobiltelefoner, som lite senkommet tillägnas Arne Brun på hans 90 års-dag, vill vi att hans insatser blir uppmärksammade och inte faller i glömska.Kring 2000 millennium skiftet pågick ett intensivt arbete i Lund med att sammanfatta och bekräfta effekterna av exponering med GSM-900 MHz mikrovågor på blod-hjärna barriären och hjärnans neuroner. Leif G. Salford, Arne Brun och medarbetare presenterade år 2003 i tidskriften Environmental Health Perspectives resultaten från en undersökning av skador på nervcellerna i råtthjärna efter exponering för mikrovågor från GSM Mobiltelefoner. Kontroller och testdjur visade alla tecken på närvao av albumin i hypotalamus, vilket år normalt och indikerar att albumin infärgningen av BBB läckaget också fungerar. Cresylviolettfärgningen avslöjade förekomst av spridda och grupperade mörka nervceller, som ofta var skrumpna och mörkt homogent färgade utan urskiljbara interna cellstrukturer. Några av dessa mörka nervceller var också albuminpositiva eller visade cytoplasmatiska mikrovakuoler som indikerar en aktiv patologisk process. År 2008 presenterades resultaten av ytterligare undersökningar av blod-hjärn barriärens permeabilitet och nervcellsskador i råtthjärnan efter en återhämtningstid på antingen 14 och 28 dagar efter 2 timmas exponering för mikrovågor från GSM-mobiltelefoner i 900 MHz-bandet. Efter 14 dagars återhämtningstid observerades albumin-läckage i BBB och albumin upptag i neuroner. Mörka neuron observerades endast hos råttor som exponerats med det lägsta SAR-värdet, 0,12 mW/kg. Efter 28 dagars återhämtnings period observerades läckage av albumin endast hos råttor som exponerats med det högsta SAR-värdet, 100 mW/kg. Däremot observerades efter 28 dagar förekomst av mörka neuron i råtthjärnor hos alla grupperna vilket korrelerade väl med neuronernas albumin upptag.I studien observeras neuro-patologiska förändringar redan vid SAR-värden så låga som 0,12 mW/kg vilket överensstämmer med våra tidigare resultat. Speciellt iögonfallande är att det högsta albumin upptaget i neuroner observeras vid den lägsta SAR nivån på 0,12 mW/kg. Frekvensen hos förekomsten av mörka nervceller ökade, jämfört med kontrollerna både efter 14 och 28 dagars återhämtning, men var endast signifikant vid 28 dagar efter exponering. Inga signifikanta tecken på förekomsten av mörka neuron observerades emellertid efter 7 dagars återhämtning.I en Fransk studie redovisad av Poulletier de Gannes och medarbetare 2009 exponerades enbart huvudet hos 16 st. Fischer 344-råttor (14 veckor gamla) för GSM-900 under 2 timmar vid SAR värden 0,14 och 2,0 W/kg. Fjorton alternatvt 50 dagar efter GSM-900 exponeringen kunde varken BBB-läckage eller förekomst av mörka nervceller upptäckas i rått hjärnorna. Deras resultat indikerar att det föreligger en väsentlig skillnad i resultaten vid helkropp exponering jämfört med exponering av endast huvudet.År 2015 presenterades en studie, stödd av Nationella Vetenskaps Akademin i Kina (NSFC), avseende albumin-läckage i blod-hjärnbarriären efter exponering med kontinuerliga mikrovågor på 900 MHz med SARvärden mellan 0,016 (hela kroppen) och 2 W/kg (lokalt i huvudet). Hos råttor som exponerats under 28 dagar observerades cellulärt ödem och neuronal cellorganell degeneration hos råttorna. Dessutom observerades med immun-färgning BBB-läckage av albumin i hippocampus och cortex. Efter exponering för 900 MHz mikrovågor under 14 respektive 28 dagar hade serum albumin diffunderat in i neuropilen mellan cellkropparna, som omger neuronerna. Upptag av Albumin i hippocampus neuron hos råttor exponerade under 28 dagar, visar förekomst av mörka neuron. Deras resultat är i linje med Lunda-resultaten som publicerades 2003 och 2008.
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