Elham Teimouri is a PhD candidate based at Edith Cowan University in Western Australia, working on a project investigating the utility of nutraceutical compounds as potential therapeutic agents in Alzheimer’s disease. Elham is supervised by Professor Ralph Martins, Dr Stephanie Rainey-Smith, Dr Prashant Bharadwaj and Associate Professor Giuseppe Verdile. At the time of writing, Elham has published one peer-reviewed scientific publication with an additional three in preparation.

Alzheimer’s disease (AD) is a progressive, fatal neurodegenerative disease characterized by extensive neuronal loss associated with increased accumulation of the beta amyloid (Aβ) protein. Reducing production, preventing aggregation and improving clearance of Aβ are areas of active research in the development of therapeutic agents to ameliorate neurodegeneration in AD. The Indian plant amla (Emblica officinalis), commonly known as Indian gooseberry, has widely been utilized in traditional Ayurvedic medicine preparations in the treatment of a variety of disease conditions including cardiovascular disease and diabetes: accumulating evidence also suggests that amla may be beneficial in AD. Amla exhibits antioxidant, anti-inflammatory, and anti-apoptotic mechanisms and more recently has been shown to modulate autophagy; a vital protein degradation pathway involved in the clearance of damaged organelles and aggregate proteins in cells. Our own recent in vitro work shows that amla extract enhances autophagy and modulates accumulation of proteolytic products of Amyloid precursor protein (APP) such as APP-C terminal fragments (C99, C83). Amla treatment (50-300 μg/ml) induced a dose-dependent increase in autophagic flux, as measured by Western blotting utilizing an LC3 directed antibody as an autophagosome marker. At similar concentrations, amla treatment also reduced accumulation of APP C-terminal fragment levels by 33 to 77%. However, no significant changes were observed in APP levels, indicating that amla did not alter APP production. Overall, our findings suggest that amla may confer beneficial effects through modulating autophagy and Aβ metabolism, and warrants further investigation as a potential therapeutic agent in AD.

Somayeh Taghizadeh is from Islamic Azad University of Ardabil, Iran.

Introduction: Women suffering from Alzheimer tend to have negative attitudes towards their own psychological changes. Negative attitudes and inappropriate adaptive reactions may effect on their Quality of life. Objective: This study aimed to investigate the effectiveness of cognitive behavioural therapy (CBT) on depression and the quality of life in women with Alzheimer. Methods: The research method was quasi experimental with pre test-post test design and control group. A sample of 34 women was selected by available sampling method as the statistical sample and was randomly assigned into two groups named control and intervention. In the intervention group, CBT was performed for 45 minutes, 1 times per week for 8 weeks. The control group did not receive any interventions (CBT) and were asked to maintain their normal treatments. The severity and perception of depression and quality of life (QoL) were measured using the Beck’s depression inventory second edition (BDI-II), and Multicultural Quality of Life Index questionnaires. Hypothesises were tested by co-variance analysis. Result: Results indicated that the post-test values have been affected by the independent variable (P<0.05). Conclusions: Cognitive behavioural therapy had positive effects on depression and quality of life for Alzheimer’s patients.

Chitra has completed her Masters in Siddha medicine from The Tamilnadu Dr.MGR Medical University, Chennai and doing Ph.D in National Institute of Siddha, Chennai under the same University and has submitted the Ph.D synopsis. She has published four papers in reputed journals.

Pũrṇa Cantirotaya Centũram (PCC) is a gold-based Siddha formulation, indicated for chronic neurological symptoms and it is in vogue for curing many diseases. PCC is composed of sulphur, mercury and gold in the ratio of 4:2:1, processed with red cotton flower and plantain stem pith further subjected to specified heat process to obtain the oxide form of metals as reddish powder (Centũram in Siddha). In the present study, PCC was investigated for its potential to improve cognitive performance in rat model. Animals were intracerebroventrically injected with streptozotocin (STZ) (750 μg/10 μl ACSF/Rat) on day 1 and 3. Sham operated received saline in the place. Animals were treated with PCC (15 and 30 mg/kg, p.o) for a period of 21 days. On days 22, they were subjected to cognitive assessment in passive avoidance apparatus. Following cognitive tests, the animals were euthanized to collect brain for mRNA expression of AChE and MChR and for histopathological examination. Animals treated with PCC for a period of three weeks showed increased transfer latency in passive avoidance test, which reveals that it restored cognitive function in STZ administered animals. Further, PCC animals showed decreased AChE and increased MChR mRNA expression, which could be the possible mechanism involved in the memory restoration. Histopathological evidences showed increased number of Nissl cells revealing the neuro protective effects of PCC. These results demonstrate the effectiveness of PCC in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer’s disease.

Jana Kynast has completed her BA and MA in Psychology at the age of 25 years from the University of Leipzig, GER. In 2014 she became a fellow of the International Max Planck Research Network on Aging and started her PhD at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig. Her research interests are the neuropsychology of mild cognitive impairment and dementia as well as its relation to neuroimaging and genetic biomarkers of dementia and dementia prestages.

Background: White matter hyperintensities (WMH) feature as a marker of long-term white matter (WM) degeneration, caused by a broad range of pathologies (see Maillard et al., 2012). WMH can be detected on T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans and progressively increase with age (de Leeuw et al., 2001). Age-related WMH are strongly associated with vascular risk factors and are assumed to cause a global decline in cognitive performance. The progression of WMH majorly affects attention and executive functioning (Kloppenburg et al., 2014). However, a comprehensive, domain-specific characterization of the neuropsychological features associated with WMH is needed to validate recent findings and to further identify cognitive patterns associated with WMH. Here, we aim at the identification of neuropsychological characteristics associated with WMH in a large, non-clinical sample. Methods: We included 850 persons participating in the study of the Leipzig Research Centre for Civilization Diseases at the University of Leipzig, Germany (M = 60 years, SD = 13.1 years, range: 21-79 years). MRI was acquired for every participant with a 3 Tesla MRI-scanner. The amount of WMH on the individual FLAIR sequences was quantified on the 4-stage Fazekas scale (Fazekas, 1987) by experienced neuroradiologists. The sample was categorized in 4 Fazekas groups. Age, sex and education were identified as confounding factors. The neuropsychological test battery included the Trail Making Test (parts A and B), the Stroop Test, the Consortium to Establish a Registry of Alzheimer’s Disease (CERAD) test battery and the 20-item Dysexecutive Questionnaire (DEX) of the Behavioral Assessment of the Dysexecutive Syndrome (BADS). Neuropsychological subtests were assigned to the cognitive domains attention, executive function, memory, learning, language, verbal fluency and perceptual-motor abilities, under well-established theoretical considerations (Beck et al., 2014; Madureira, 2006) and with respect to the clinical diagnostic criteria for mild and major neurocognitive disorder (DSM-5, American Psychiatric Association, 2013). Individual test results were age-standardized (M = 0, SD = 1) to the mean of the corresponding age group (<65 y, 66-69 y, 70-74 y, 75+ y). Age-standardized scores corresponding to the same cognitive domain were averaged to seven cognitive domain scores indicative of objective cognitive performance (see Madureira, 2006). A content based categorization of DEX items to five cognitive domains (attention, executive function, memory, language and social cognition) was applied. The sum score for every domain was age-standardized to the mean of the corresponding age group. Differences between the four Fazekas groups in (1) objective cognitive performance (7 measures) and (2) subjective cognitive complaint (5 measures) were analyzed with the nonparametric rank-sum test with data-alignment (critical alpha level: p < .05; see Bortz et al., 2008). Data was aligned for the effects of sex and education and their interaction with Fazekas score. Data was corrected for identical ranks. Group differences were examined using the single comparison algorithm proposed by Schaich & Hamerle (1984; see Bortz et al., 2008). For single comparisons, the alpha level was adjusted due to multiple comparisons (critical alpha level: 0.005). Results: A general decline in cognitive performance is associated with a higher Fazekas score. The decline in cognition becomes evident with higher lesion load (starting at Fazekas score 2). Fazekas groups significantly differed in performance measures of attention (χ²(3,846) = 13.77, p < .01) and executive functions (χ²(3,846) = 12.84, p < .01). Analyses yielded marginally significant group differences in objective measures of memory (χ²(3,438) = 7.74, p = .05) and visuoconstructive abilities (χ²(3,434) = 7.73, p = .05). In all four cognitive domains, performance significantly declines with larger WM lesion load (Fazkas score 2), while low lesion load (Fazekas score 1) was not associated with a decline in cognitive performance. Fazekas groups significantly differed in measures of memory complaint (χ²(3,796) = 18.8, p < .001) and complaint on executive function (χ²(3,796) = 39.88, p < .001). For both measures, persons with low lesion load (Fazekas score 1) worried significantly less than healthy persons (Fazekas 0) and persons with larger lesion load (Fazekas score 2, 3). Conclusion: Results show a substantial decline in cognitive performance with larger lesion load, which becomes evident at progressed stages of WMH (starting from Fazekas score 2). In line with recent literature (Kloppenborg, 2014), attention and executive function are assumed to be major dimension of cognitive decline. Furthermore, results suggest that small, punctual lesions (Fazekas score 1) are less likely to be associated with impaired cognitive performance. A similar relation has also been found for subjective cognitive performance. Memory and executive functions are majorly affected by WMH and correspond to the results of objective cognitive performance. Surprisingly, persons with small WM lesions tend to be less worried about their cognitive performance than healthy persons. However, larger lesion load (Fazekas score 2 & 3) was associated with increased subjective complaint. This large cohort study contributes to the framework of age related WM changes and their association with domain specific cognitive performance and subjective cognitive complaints.

Sanam Zulfiqar is working for health care professional need to make significant strides in alleviate their disease progression and improve their quality of living.

Emerging challenges by health care professionals in providing quality of life (QOL) to Alzheimer’s and Dementia patients: A Systemic Review

Kay Donnellon is a senior lecturer within the University of Cumbria in advanced clinical practice and palliative care in both undergraduate and post graduate programmes. After a long career in community and primary care, palliative care has remained a passion and has allowed her to develop collaborative working arrangements with local hospices assisting in accrediting modules with them. She is a current PhD student researching quality in out of hours services where she is an active member of her local clinical governance group as well as an Advanced Nurse Practitioner.

As a consequence of an increasing elderly population the incidence of those living and dying with dementia is increasing with demands for quality care throughout the health and social care sector. This study involved delivery of workshops to care home staff specifically for improving communication and comfort measures at end of life for people with dementia and evaluating their effect three months later to assess whether these approaches had been embedded into practice. Semi structured interviews were undertaken 3 months following the workshops to assess whether practice had been effected by the skills and knowledge developed in the workshops. A number of themes emerged including listening and understanding; peer support; empowerment and confidence; communications; making an early start; building trust, the wider team and documentation. Through promoting confidence in the approaches they were taking and a realisation that communicating is the core of compassionate care the care home staff were empowered to provide effective multidisciplinary palliative care for their residents with dementia. This team approach ensured appropriate support was available at end of life within these care homes where the person wished to be with familiar people and surroundings which ultimately promoted client choice.

Kay Donnellon is a senior lecturer within the University of Cumbria in advanced clinical practice and palliative care in both undergraduate and post graduate programmes. After a long career in community and primary care, palliative care has remained a passion and has allowed her to develop collaborative working arrangements with local hospices assisting in accrediting modules with them. She is a current PhD student researching quality in out of hours services where she is an active member of her local clinical governance group as well as an Advanced Nurse Practitioner.

Background: Nine out of 10 of those aged 65 and older are suffering from multiple chronic conditions (MCC). Moreover, about 9% of all people 65 years of age and older having some form of dementia. Little is known about how family caregivers and health-care providers deliver person-centered palliative care for community-dwelling older adults with MCC including dementia. This study presents a phonological study of the lived palliative care experiences of community-dwelling older adults with MCC, including dementia and their care teams. Hypotheses/Objectives: This study seeks to examine the lived palliative care experiences of community-dwelling older adults with comorbidities including a dementia to understand the significant factors of the care environment that contribute to quality palliative care for community-dwelling individuals. Proposed Methods: Data will be obtained from semi-structured interviews with community-dwelling individuals with dementia and their informal and formal caregivers. Interviews will be coded and analyzed using the principles of Hermeneutic Phemonology. Future Applications/Directions: This study will result in a better understanding of how older adults and their care teams are managing multiple chronic conditions coexisting with dementia and their preferences for care. Understanding common patterns of preferences for care can help to guide the design of a community-based, dementia-specific model of palliative care within South Western Ontario.

Lisa has a Master degree in Care of Elderly People and is currently enrolled in a PhD programme at the University of Technology, Sydney. Her long-held passion to improve the quality of care for elderly people, especially those living with dementia has been realised in her numerous contributions across public health and community organisations which have advanced knowledge in the area and improved access to dementia care for older people with culturally and linguistically diverse backgrounds, especially to the Chinese community. Her work can be evidenced by the Northern Sydney Community Award by Australian government in 2014.

Introduction: Due to cultural barriers, caregivers with culturally and linguistically diverse backgrounds looking after people with dementia experience difficulties in their care-giving role and access to services (1). Carer support is important in maintaining the home-based care for people with dementia and delaying institutionalization. Aim: To provide support to Chinese carers for people living with dementia and to describe their experience in the community carer support program. Method: Monthly carer support program were conducted after the Community Carer Coaching Project (2) since April, 2013 with the aim to translate knowledge into practice. Data was collected during the monthly meetings. NVivo and thematic analysis were used to analyse the data. Results: One male and 19 female Chinese carers participated in monthly carer support program (n=20). Sixty per cent of carers were spouses and 40% were children. Six themes emerged from the analysis which included: ‘sharing of information and helping each other’, ‘eagerness to seek help’, ‘carers looking after their own health’, ‘acceptance and confidence in the caring task’, ‘developing person-centred caring skills’ and ‘positive thinking and psychological empowerment’. Conclusion: Qualitative analysis of this carer support program showed perceived benefits of carers in improving their knowledge and skills in person-centred care, and confidence in the caring task. It is important to support these carers in the community to minimize institutional care for their family members living with dementia.

Andrew McKinnon from Macquarie University, Department of Psychology, Australia. He is currently working as a Research Officer, Exam Supervisor in Macquarie University.

Participants underwent resting-state fMRI along with comprehensive neuropsychological, medical and psychiatric assessment. Self-report data was collected including sleep quality assessment via the Pittsburgh Sleep Quality Index (PSQI). Relative to those without sleep disturbance, sleep-disturbed MCI participants demonstrated significantly diminished DMN connectivity between: a) the retrosplenial cortex and lateral temporal cortex, a finding that was replicated in our amnestic MCI (aMCI) subgroup; b) the lateral temporal cortex and the posterior inferior parietal lobule; c) the parahippocampal cortex and hippocampal formation; and d) the temporal pole and the parahippocampal cortex. Additionally, the aMCI sleep-disturbed subgroup showed significantly diminished connectivity between the temporal pole and the hippocampal formation. Conclusions: Sleep disturbance in MCI and its amnestic subtype is associated with DMN functional connectivity deficits in brain regions underpinning salient memory and sleep systems. Future studies should aim to build on these results via experimental manipulation and objective measurement of sleep.

Zahra Abbasskhani from Department of Biological Sciences, Institute for Advanced studies in Basic Sciences, Zanjan, Iran

Alzheimer's disease and lysozyme amyloidosis are associated with the formation of protein aggregates. Mounting evidences support the idea that endogenous ‘biometals’, such as copper, iron, zinc and exogenous metals such as aluminum, can be involved in the pathogenesis of a variety of neurodegenerative diseases. In order to clarify further this issue, we investigated the effects of different concentrations of these metal ions on the formation of fibrillar and nonfibrillar forms of beta amyloid peptide (Aβ) and lysozyme. We made use of thioflavin T fluorescence and atomic force microscopy (AFM) to study the effect of metal ions on Aβ aggregation after incubation at 25 0C for 24hr. Our results showed that the stoichiometric and super-stoichiometric concentrations of Cu (II) lead to decreases in ThT fluorescence of Aβ and hence prevented fibril formation while the sub-stoichiometric concentration of Cu (II) lead to increased ThT fluorescence of Aβ peptides. On the other hand, the super-stoichiometric, stoichiometric and sub-stoichiometric concentrations of Fe (III) resulted in an increased ThT fluorescence. All three concentrations of Al (III), like Fe (III), led to increased ThT fluorescence of Aβ peptides and increased formation of protein aggregates. All three concentrations of zinc ion led to decreases in ThT fluorescence and hence there was a decrease in Aβ fibril formation. In all cases the AFM images were also prepared and confirmed the fluorescent results. To study the effect of metal ions on the rate of accumulation, using hen egg-white lysozyme (HEWL) as a model system to induce aggregation, we sat out to investigate how metal ions influence amyloid formation. We made use of thioflavin T fluorescence and circular dichroism to study the influence of Zn (II), Cu (II) and Al (III) on HEWL aggregation after incubation at 540 C for 1, 2, 4, 8, 12, 16, 24, 48, 72 and 144hr, at stoichiometric concentrations. The kinetics of fiber formation typically followed a sigmoidal fiber growth curve, including a lag-phase (nucleation) and a growth rate (elongation). Our results show that Cu (II), Zn (II) and Al (III) reduce the lag period, allowing the aggregation process to essentially “bypass” the critical nucleation phase, often considered the rate limiting step in aggregation in non-metallic solutions, at stochiometric concentrations. The presence of these metals induced the formation of amorphous aggregates.

Jaspreet Kaur is from Chandigarh College of Pharmacy, India

The study was aimed at investigating the effect of Coleus forskohlii on memory deficits associated with Alzheimer’s type dementia in rats. Dementia was induced with chronic administration of a high fat diet (HFD) in separate groups of animals. Memory of the animals was assessed by the Morris water maze (MWM) test. Brain thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels were measured to assess total oxidative stress. Brain acetylcholinesterase (AChE) activity and total serum cholesterol levels were also measured. HFD produced a significant impairment of learning and memory. Higher levels of brain AChE activity and TBARS and lower levels of GSH were observed in HFD-treated animals. HFD-treated rats also showed a significant increase in total serum cholesterol levels. Administration of Coleus forskohlii not only lowered HFD-induced rise in total serum cholesterol level but also attenuated HFD-induced memory deficits. Further Coleus forskohlii administration also reversed HFD-induced changes in biochemical level. This study demonstrates the potential of Coleus forskohlii in memory dysfunctions associated with experimental dementia and provides information of involvement of Pregnane X receptors(PXR).

Li Yong is from Sichuan Provincial Center for Disease Control and Prevention, China

Objective: The relationship of the selenium content in blood and nail of rural old people and the APOE genotype, as well as their age was investigation with the difference comparison and correlation analysis. Methods: Five hundred subjects were studied in the low selenium areas of Sichuan province (Jiange city) and the appropriate selenium area (Qionglai city) . The age of the old people with different genotype in the low selenium area and the appropriate selenium area was compared with the variance analysis method . Following the principle of voluntary participation, the blood and nail samples was collected from fifty subjects in two areas. After that, selenium content of these samples were determined to investigate the relationship of APOE genotype, selenium content and age in low selenium areas and appropriate selenium area . The correlation coefficient method was used for data analysis... Results: The significant difference was found for the age between the old peoples with ε 2/2 geno and those of having not this gene in 1000 subjects (P < 0.05). But the same results were not seen in, the other genes (2/3, ε 2/4, ε 3/3, ε 3/4, ε 4/4). There was a correlation between genotype, age and the selenium contents of nail and blood in 50 subjects. Futhermore, there was a strong correlation between the blood selenium and the age of rural old people (P=0.198, at 0.05 level (bilateral)). And the results showed that the selenium contents in blood of subjects with gene ε2 were higher those of having not genotypes ε2. Conclusion:. The life time of people could be extented with increasing the selenium content in the body .

Ping Li is from Sichuan Provincial Center for Disease Control and Prevention, China

Objective To investigate the relationship of depression degree in aged population and selenium content to APOE gene polymorphism in deferent selenium level areas. Methods Choose two rural areas, appropriate selenium level (Qionglai) and low selenium level (Jiange); Selecte 500 volunteers over 65 by cluster sampling method, to carry out the Geriatric Depression Scale (GDS).and relevant cognitive questionnaire respectively. Nails and finger blood are sampled simultaneously to detect the selenium level and APOE gene, 50 volunteers are required to sample vein blood for detecting blood selenium level. Evaluate the depression degree by continuous GDS score (scores between 11 and 20 are generally considered to represent significant mild depression and scores of 21 or higher are considered severe depression). Difference between different areas on distribution of depression degree, nail’s selenium content and APOE gene polymorphism is tested by t test and chi-square test. Results Results from two areas show good correlations between blood selenium and nail selenium level. Significant statistical differences are observed between two areas both in nail selenium level（P＜0.001） and distribution of APOE gene polymorphism（P＜0.0001）. Difference of constituent ratio of depression degree is significant too, in which the number of depression patients in Jiange is more than that in Qionglai. Divide all 1000 subjects into two groups according to the nail selenium content (group 1 with nail selenium content <0.259μg/g and group 2 >0.259μg/g). The frequency of geneε2/2、ε2/4、ε3/4 in group 1 is lower than group 2, with significant difference（P＜0.05）. The ratio of alleleε2、ε3、ε4 in group 2 is higher than group 1, with statistical difference. Ratios for Alleleε2、ε3、ε4 of APOE are significant different either in different areas or different nail selenium content groups. As for the distribution of gene polymorphism comparison, all five genotypes have statistical difference in different area groups, but only three of them (ε2/2, ε2/4, ε3/4) have statistical difference in nail selenium content groups. Conclusions Population’s selenium levels are different in different selenium level areas. There is correlation between selenium level and APOE gene polymorphism, geneε2/2 only appears in population with higher selenium content. Patients of depression in lower selenium area are more than that in area with higher selenium level, which shows the possibility of selenium being risk factor for aged depression.

Yunliang Guo is from Hospital of Qingdao University, China

This paper aimed to explore the protective effects of picroside II against the neuronal apoptosis and changes in morphology and structure that follow cerebral ischemic injury in rats. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion (MCAO) in 60 Wistar rats, and intraperitoneal injections of picroside II (20 mg/kg) were administered. The neurobehavioral functions were evaluated with the modified neurological severity score (mNSS) test. The cerebral infarct volumes were measured with tetrazolium chloride (TTC) staining. The morphology and ultrastructure of the cortical brain tissues were observed with hematoxylin-eosin staining and transmission electron microscopy, respectively. The apoptotic cells were counted with terminal deoxynucleotidyl transferase dUTP nick-end labeling and flow cytometry, and pERK1/2 expression was determined by immunohistochemical assay. The results indicated that neurological behavioral malfunctions and cerebral infarcts were present in the MCAO rats. In the model group, the damage to the structures of the neurons and the blood brain barrier (BBB) in the cortex was more severe, and the numbers of apoptotic cells, the early apoptotic ratio (EAR) and pERK1/2 expression were significantly increased in this group compared to the control group (P<0.05). In the treatment group, the neurological behavioral function and the morphology and ultrastructure of the neurons and the BBB were improved, and the cerebral infarct volume, the number of apoptotic cells, the EAR and pERK1/2 expression were significantly decreased compared to the model group (P<0.05). These results suggest that picroside II reduced apoptosis and improved the morphology and ultrastructure of the neurons and the BBB and that these effects resulted in the recovery of the neurobehavioral function of rats with cerebral ischemia.

Haleh Tajadini is from University of Medical Sciences, Iran

Avicenna has categorized injuries of brain as 'afate zehn' (brain disorders) and has described them as 'Fisad-e- zekr','Fisad-e- fekr', and 'fisad-e- khiyal' that are similar to the staging of Alzheimer disease and accordingly, has suggested some therapies for them too. The causes of these diseases from Avicenna's viewpoint are: simple coldness, coldness with dryness or wetness and rarely hotness. Avicenna has discussed brain disorders based on the theory of the four humors. This article examines the definition, etiology and clinical manifestations of Alzheimer disease based on Ibn Sina's work: 'The Canon of Medicine'.

Reham Abdel-Kader has completed her PhD in 2009 from Goethe University in Frankfurt and is currently a post-doc in the German University in Cairo, Egypt. She has earned her degree in Pharmacology and her major research interest is mechanisms and treatment of Alzheimer’s’ disease. Reham has supervised a number of MSc theses, and is currently supervising and co-supervising several Msc. and PhD theses in the field of Alzheimer’s disease. Her most recent publication was titled “Methylene Blue Improves Brain Mitochondrial ABAD Functions and Decreases Aβ in a Neuroinflammatory Alzheimer’s disease Mouse Model“which was published in Molecular Neurobiology (Jan 2015).

Neuroinflammation plays a critical role in many chronic inflammatory diseases such as Alzheimer’s disease. The early inflammatory response is characterized by microglial activation and behavioral impairment, often accompanied by degeneration of neurons. Src family kinases (SFKs) are involved in the regulation of innate immunity and are key regulators of toll-like receptor- 4 (TLR4) inflammatory signaling. Dasatinib, a SFKs inhibitor was used in this study to explore the influence of Src kinases in TLR4 pathway and their effect on cognition, microglial activation phenotypes, astrocytosis and neurodegeneration in an in vivo LPS model. Adult male Swiss albino mice were treated with intraperitoneal injection (i.p) of dasatinib (5 mg/kg) 1 hour prior to i.p administration of LPS (250 µg/kg). Four hours following LPS, dasatinib improved the spatial working and recognition memory determined by Y-maze and novel object recognition tests respectively. The LPS-induced mRNA levels of M1 marker CD86 and M2 marker arginase-1 were assessed in brain tissue by RT-qPCR and both were significantly inhibited by dasatinib. Astrocytosis was reversed by dasatinib pretreatment in correlation with attenuated neurodegeneration which were assessed using immunohistochemistry (IHC) and Hematoxylin and Eosin staining respectively. Moreover, dasatinib suppressed MyD88 protein levels in parallel with inhibition of Src protein expression shown by IHC. These findings suggest that dasatinib may be useful in dementia and neuro-inflammation through modulating glial cells activation, enhancement of cognitive functions and limiting neurodegeneration. These results highlight the involvement for Src kinases in TLR4/MyD88 cascade, showing the possible therapeutic role of dasatinib in neuro-inflammatory diseases.