Alzheimer’s disease is a progressive neurodegenerative disorder leading to dementia. Interestingly, AD is more prevalent in women than men, where two third of the diagnosed AD population is female. The underlying neuropathology is characterized by extracellular A𝛽 plaques and intracellular tau tangles leading to neuronal cell death. The hippocampus, the main site for learning and memory exhibits the most significant neuronal loss in AD. It is also one of the primary neurogenic niches in the adult brain. A decline of hippocampal neural stem cells is a common feature of AD indicating a defect in neurogenesis. To model AD neuropathology, a triple transgenic model of AD (3xTg) was used. We hypothesize that the defects associated with adult neurogenesis precede the onset of AD hallmarks. Our data showed that neurogenesis defects are present as early as post-natal day 5 of age in the 3xTg model of AD, well before the development of the neuropathology. The early defects were also observed in the TgCRND8 model of AD at 3 months of age. Moreover, no statistically significant difference was detected between male and female mice at 3 months and 9 months of age when investigating NSC populations. This could indicate that sex may not need to be taken in consideration in research design when investigating NSC decline in 3xTg mice. These findings are of clinical relevance, as they may identify early changes that may open opportunities for therapeutic interventions aiming at preventing or delaying neurodegeneration.

Alzheimer’s disease (AD) is a neurodegenerative disease classified pathologically by the presence of tau tangles and amyloid plaques. The largest genetic risk factor for AD is the APOE ε4 allele, while the APOE ε2 allele has been linked to a protective effect for AD. Recent studies demonstrated that APOE genotypes are linked to unique omics signatures and pathological features relating to AD, such as blood-brain barrier breakage. To investigate the role of APOE genotype in AD, I analyzed different levels of omic data in blood and brain. I analyzed transcriptomic data derived from autopsied brains using network and differential gene expression approaches to identify genes and pathways involved in the APOE ε2 protective mechanism for AD. Additionally, I identified APOE genotype-specific pathways and networks involved in both blood and brain function in AD using blood and brain tissue gene expression from mostly the same individuals. Lastly, I analyzed the association of methylation of DNA from blood and brain samples with AD to identify APOE and AD specific methylation signatures and potential drug targets. Collectively, this thesis emphasizes the utility of investigating APOE genotypes individually to identify novel pathways and potential drug targets within AD subpopulations.

TREM2 is an innate immune receptor expressed in microglia and macrophages. ApoE isoforms (E2/E3/E4) are ligands of TREM2. TREM2 variants and ApoE4 are top risk factors of Alzheimer’s disease. TREM2 can be cleaved from cell membrane as soluble TREM2 (sTREM2), the level of which fluctuates during Alzheimer’s progression. However, the mechanisms that sTREM2 and the interactions between TREM2 and ApoE may contribute to Alzheimer’s neuroinflammation are largely uncharacterized. The project objectives were to investigate whether sTREM2 and ApoE isoforms can affect cytokine expression profiles in myeloid-derived cell models. My results show that sTREM2 can stimulate inflammatory cytokine expression at early time-point but anti-inflammatory cytokine expression at later time-point mainly via MAPK-JNK signaling pathway. sTREM2 has differential effects on cytokine expression in M0, M1, and M2 macrophages. ApoE isoforms also differentially induce cytokine expression and regulate TREM2 expression in M0, M1, and M2 macrophages. My study reveals a complex interplay of sTREM2, TREM2 and ApoE isoforms and differential effects of those in the models.

An environment strongly influences the behavior of individuals with dementia. A well designed physical environment can maintain and enhance the ability to function and improve quality of life. My thesis uses a residential environment for people suffering from dementia as the basis for therapeutic intervention. Understanding the physical and psychological effects of architecture on a person with dementia is an important tool in slowing the progression and effects of the disease. The competence of an individual can effect how he or she experiences a space and can make them respond more intensively to the immediate environment. Building orientation, color, lighting, and access to nature can affect the psyche of a resident and can help stabilize and reduce the effects of the disease. / Master of Architecture

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / There is growing evidence of the burden of family care giving, particularly among spouses. but little attention has been paid to the gratifications experienced. A cross-sectional, non-probability, interview study conducted in Massachusetts of 50 wives ages 58 and older supports the hypothesis that caregivers who are more gratified have greater well-being and those who experience greater frustration are more distressed. The caregivers were gratified by having their husbands at home; by believing that caregiving involved reciprocity and nurturing; enjoying moments of warmth. comfort, and pleasure: having gratification from their emotional support systems; and experiencing no change in marital closeness since the illness. Caregivers at risk of mental health problems are those who are highly frustrated and not gratified by the care giving experience. The general frustrations of feeling overwhelmed, resentful, fearful and not resigned were associated with low well-being. Frustration of wives with husbands' ADL ability, with inadequate time for themselves. with constraints of caregiving, with household chore responsibility. and with changes in their emotional support systems also contributed to low well-being. Comparison of the sample with national studies all utilizing the Dupuy WellBeing Scale, shows that the majority of caregivers are in no more distress than the general adult population. Thirty-two percent, however, are in severe distress. Caregiver distress is associated primarily with anxiety, not with depression as widely believed. Distress is not associated with caregiver age or health or with patient illness characteristics, factors that should no longer be used in clinical circles to assess the status of caregivers. Maintaining continuity in preferences and patterns is important to the well-being of caregivers. The study findings can guide the mental health treatment of caregivers particularly as the data lends support to the theory that disruption in the lives of caregivers is a stressor. / 2999-01-01

No / The objective of this study was to investigate whether the presence of depressive symptoms influences the clinical expression of Alzheimer's pathology. We have analysed the relationships between the severity of Alzheimer's pathology and cognitive decline in two patient groups defined by the presence or absence of depressive symptoms. The study included 89 subjects who participated in a longitudinal research programme prior to death, underwent post-mortem examination and were found to have only Alzheimer-type pathology in their brains, ranging in severity from the entorhinal to neocortical stages. Our results indicate that depressive symptoms did not influence cognition in the early (entorhinal) stages of Alzheimer's disease (AD; where cognition was good regardless of whether or not there was evidence for depressive symptoms) or in the late (neocortical) stages (where cognition was poor regardless of whether or not there was evidence for depression). However, in the intermediate (limbic) stages, patients with depressive symptoms had significantly worse cognitive performance (mean CAMCOG of 32) than those who did not (mean CAMCOG of 73). We conclude that depressive symptoms may contribute to the cognitive decline of AD patients in that pathology, that would be otherwise silent, becomes clinically apparent. Therefore, a multiple diagnosis of early AD and depression should be more widely considered in elderly persons presenting with mild cognitive decline and depression. Treating the depressive symptoms would benefit the patient, but the cognitive improvement may not indicate that AD is absent.

The purpose of the present study was to compare 42 community-dwelling spouse and child Alzheimer's Disease caregivers with 38 community-dwelling potential caregivers on salience of illness symptoms, and accuracy of judging symptoms of illnesses.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2002. / Includes bibliographical references (leaves 167-185).

Background: Alzheimer’s disease, one type of dementia, is predicted to have great impact on society and economy. This effect increases rapidly especially in developing countries. The number of people with Alzheimer’s disease is huge due to the large population in China where the effects of this disease are amplified by the one-child policy. Objective: To review the risk factors of Alzheimer’s disease in different countries and offer some suggestions that how to prevent Alzheimer’s Disease in China that has very limited research on Alzheimer’s disease. To make recommendations for potential strategies to be implemented by policy-makers, government or other stakeholders. Method and results: Relevant studies which identified the risk factors for Alzheimer’s disease and evaluated the interventions and treatments for reducing the risk of getting Alzheimer’s disease, that were published between 1990 and 2012 were searched in PubMed and Google Academic using specific keywords. A total of 1071 studies were found and 62 used. Based on this systematic review, the risk factors of Alzheimer’s disease are age, lifestyle, family history and genetics, vascular, mild cognitive impairment, head injury as well as early-life negative events. There appear to be several important contributions to Alzheimer’s disease prevention including diet, cognitive activity, physical activity, social engagement, smoking cessation, and alcohol ingestion or simply being optimistic. Conclusion: This review has included the potential risk factors of Alzheimer's disease and the ways of preventing Alzheimer's disease, as well as to produce some possible strategies of preventing Alzheimer's disease based on the situation in China for the Chinese government and policy makers such as to use media as an important channel to draw people's attention about Alzheimer's disease and to educate about preventive factors. There should be government-funded education and health services in the rural areas and plans to build more leisure and sports centers in China. The government should also subsidize hospitals and medical centers to provide affordable or even free health examinations for people and build a central database for the purpose of recording, analysis and research into Alzheimer's disease for better understanding of the disease. Medical professionals and volunteers can help to enhance this database by the implementation of data collection to look for symptoms of Alzheimer’s disease. If the patients appear to have such symptoms, further data collection should be taking place, such as family history of Alzheimer’s disease, health status, head injuries, family status, characteristics and behavior, income levels, residential areas and other background information of the patients as part of their work whenever and wherever they go, especially in rural areas. / published_or_final_version / Public Health / Master / Master of Public Health

Thesis (Ph. D.)--Michigan State University. Dept. of Psychology, 2006. / Title from PDF t.p. (viewed on Nov. 16, 2008) Includes bibliographical references (p. 71-78). Also issued in print.