Recent discoveries widen the basis for future research in Alzheimer´s disease.

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

Blood-brain barrier permeability in rats exposed to electromagnetic fields used in wireless communication

iological effects of radio frequency electromagnetic fields (EMF) on the blood-brain barrier (BBB) have been studied in Fischer 344 rats of both sexes. The rats were not anaesthetised during the exposure. All animals were sacrificed by perfusion–fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter perfusion fixed with 4% formaldehyde for 5–6 minutes. Whole coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 m. Albumin and fibrinogen were demonstrated immunohistochemically and classified as normal versus pathological leakage. In the present investigation we exposed male and female Fischer 344 rats in a Transverse Electromagnetic Transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with different pulse power and at various time intervals. The CW-pulse power varied from 0.001 W to 10 W and the exposure time from 2 min to 960 min. In each experiment we exposed 4–6 rats with 2–4 controls randomly placed in excited and non-excited TEM-cells respectively. We have in total investigated 630 exposed rats at various modulation frequencies and 372 controls. The frequency of pathological rats is significantly increased (p < 0:0001) from 62=372 (ratio: 0:170:02) for control rats to 244=630 (ratio: 0:390:03) in all exposed rats. Grouping the exposed animals according to the level of specific absorbed energy (J/kg) give significant difference in all levels above 1.5 J/kg. The exposure was 915 MHz microwaves either pulse modulated (PW) at 217 Hz with 0.57 ms pulse width, at 50 Hz with 6.6 ms pulse width or continuous wave (CW). The frequency of pathological rats (0:17) among controls in the various groups is not significantly different. The frequency of pathological rats was 170=481 (0:350:03) among rats exposed to pulse modulated (PW) and 74=149 (0:500:07) among rats exposed to continuous wave exposure (CW). These results are both highly significantly different to their corresponding controls (p < 0:0001) and the frequency of pathological rats after exposure to pulsed radiation (PW) is significantly less (p < 0:002) than after exposure to continuous radiation (CW)

Brain tumour growth in rats exposed to electromagnetic fields used in wireless cellular communication

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

Finite volume approach for the instationary Cosserat rod model describing the spinning of viscous jets

The spinning of slender viscous jets can be described asymptotically by one-dimensional models that consist of systems of partial and ordinary differential equations. Whereas the well-established string models possess only solutions for certain choices of parameters and set-ups, the more sophisticated rod model that can be considered as $\epsilon$-regularized string is generally applicable. But containing the slenderness ratio $\epsilon$ explicitely in the equations complicates the numerical treatment. In this paper we present the first instationary simulations of a rod in a rotational spinning process for arbitrary parameter ranges with free and fixed jet end, for which the hitherto investigations longed. So we close an existing gap in literature. The numerics is based on a finite volume approach with mixed central, up- and down-winded differences, the time integration is performed by stiff accurate Radau methods

A Factor Analytic Approach to Symptom Patterns in Dementia

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

S-100 protein levels in the blood of Fischer rats exposed to 915 MHz CW-microwaves and magnetic fields.

EnglishPersson, B. R. R., Nittby Redenbrant, H., Malmgren, L., Brun, A., and Salford, L. G. (2020). S-100 protein levels in the blood of Fischer rats exposed to 915 MHz CW-microwaves and magnetic fields. Acta Scientiarum Lundensia, Vol. 2020-005, pp. 1-9, ISSN 1651-5013Abstrakt.Syftet var att studera nivån av S-100 i blodprover som tagits från Fischer-344-råttor efter exponering för 915 MHz CW-mikrovågor och ELF-magnetfält i TEM-celler. Magnetfältsexponering ägde rum med TEM-cellen i ett Helmholtz-spolarrangemang med antingen 50 Hz sinusformat magnetfält på 5 µT eller inkoherent magnetfältbrus IMF med en maximal amplitud på 50 µT.Det verkar inte finnas någon signifikant förändring i S-100-koncentrationen i blod hos råttor som exponerats under 6 timmar för höga nivåer (4W) av kontinuerlig våg (CW) 915MHz mikrovågor, 50Hz sinusformade magnetfält (5µT) och osammanhängande magnetfält (IMF) vid 50µT. Däremot indikerar resultaten av den kombinerade exponeringen CW + IMF en minskad koncentration av S100 i blod.Minskningen överensstämmer med resultaten av en undersökning under 2010 att de extremt lågfrekventa (ELF) magnetfälten från fläktmotorn (50Hz AC, 0,3-1,5 T) minskade det förväntade BBB-läckaget av albumin på grund av mikrovågsexponering .Resultaten från andra studier indikerar också att bioeffekter orsakade av exponering för mikrovågor reduceras genom överläggning med extremt lågfrekventa magnetfält ELF. Det är därför av yttersta vikt när man undersöker bioeffekter från mikrovågor för att också kontrollera nivåer och frekvenser av lågfrekventa magnetfält i omgivningen, vilket kan vara en av anledningarna till den breda spridningen i de rapporterade resultaten

Non-thermal" Effects on the Blood-Brain Barrier in Fischer rats by exposure to microwaves

Effect of 915 MHz electromagnetic fields (EMF) on the blood brain-barrier (BBB) permeability has been studied in Fischer 344 rats of both sexes. Male and female Fischer 344 rats were exposed in a Transverse Electromagnetic Transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with different pulse power and at various time intervals. The CW-pulse power varied from 0.001W to 10 W and the exposure time from 2 min. to 960 min. In each experiment we randomly placed 4 rats in excited and 4 control rats in non-excited TEM-cells respectively. The rats were not anaesthetised during the exposure. The rats were exposed to 915 MHz microwaves, either continuous wave (CW) or pulse modulated at 4,8,16 or 217 Hz with 0.57 ms pulse width, or pulse modulated at 50 Hz with 6.6 ms pulse width as well as from a real GSM-900 telephone. All animals were sacrificed by perfusion-fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were then perfused, first with saline for 3-4 minutes, and then with 4% formaldehyde for 5-6 minutes. Whole coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. The degree of albumin leakage was demonstrated immune-histo-chemically and classified in order of increased number of albumin extravasations by a rank number: 0 - 0.5 - 1.0 - 1.5 - 2 - 3. Pathological albumin leakage was judged as albumin extravasations equal to or larger than 1. The frequency of pathological rats in all control groups was about 17%. Among rats exposed to pulse modulated microwaves the ratio of pathological rats was 170/481(0.35±0.03) and among rats exposed to continuous wave exposure (CW) it was 74/149 (0.50±0.07). These results are both highly significantly different to their corresponding controls (p<0.0001). The rats were exposed to SAR various values: 0.2; 2; (20-40); (100-500); (1000-3000) mW/kg. In the 217 Hz modulated group (GSM simulated) we found the most increased ratio of albumin extravasations OR= 4 at 0.2 mW/kg. But no significant increased ratio at SAR 2000 mW/kg. The response curve of OR versus log(SAR) had the shape of a bathtub, with a minimum at a100 mW/kg. A similar curve was recorded for OR versus Specific Absorbed Energy (SAE Joule / kg) with a minimum at 100 J/kg. Similar response curves were recorded for the various modulation frequencies 4; 8; 16; 50 Hz. We found no pronounced difference between the various modulation frequencies other than the effect of CW exposure seems to be more effective than pulse modulated exposure in opening the BBB at high SAR values 100-2000 mW/kg. Conclusion: The opening of the BBB is most effective at SAR values in the range of 0.1-0.5 mW.kg-1 and less effective in the range of 50-500 mW.kg-1. In this low SAR range thermal effects are unlikely. Thus there seems to be a non-thermal mechanism involved triggering the opening of the BBB

Nerve cell damage in mammalian brain after exposure to microwaves from GSM mobile phones.

The possible risks of radio-frequency electromagnetic fields for the human body is a growing concern for our society. We have previously shown that weak pulsed microwaves give rise to a significant leakage of albumin through the blood-brain barrier. In this study we investigated whether a pathologic leakage across the blood-brain barrier might be combined with damage to the neurons. Three groups each of eight rats were exposed for 2 hr to Global System for Mobile Communications (GSM) mobile phone electromagnetic fields of different strengths. We found highly significant (p< 0.002) evidence for neuronal damage in the cortex, hippocampus, and basal ganglia in the brains of exposed rats