Microarray Analysis in Alzheimer's Disease and Normal Aging

Ricciarelli, Roberta; d’Abramo, Cristina; Massone, Sara; Marinari, Umberto M.; Pronzato, Maria Adelaide; Tabaton, Massimo

doi:10.1080/15216540412331286002

Cited by 82 publications

(55 citation statements)

References 30 publications

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“…AD is associated with widespread transcriptional changes (27,28,(35)(36)(37)(38), which can be rationalized in part by the presence Significance Alzheimer's disease is a neurodegenerative disorder whose molecular origins have been associated with the dysregulation of a set of metastable proteins prone to aggregation. Under conditions of cellular and organismal health, the protein homeostasis system prevents effectively the misfolding and aggregation of these metastable proteins.…”

Section: Resultsmentioning

confidence: 99%

“…This protein homeostasis system is comprised of a variety of components, including molecular chaperones, the proteolytic, ubiquitin-proteasome and autophagic degradation pathways, cellular trafficking, and other elements of the cellular stress response (3)(4)(5)(6)(21)(22)(23)(24)(25)(26). The progressive decline of the efficacy of these regulatory processes upon aging is likely to contribute to the increased susceptibility of the elderly population to ageassociated neurodegenerative disorders (3)(4)(5)(6)(21)(22)(23)(24)(25)(26)(27)(28).…”

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confidence: 99%

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Protein homeostasis of a metastable subproteome associated with Alzheimer’s disease

Kundra

Ciryam

Morimoto

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Alzheimer's disease is the most common cause of dementia. A hallmark of this disease is the presence of aberrant deposits containing by the Aβ peptide (amyloid plaques) and the tau protein (neurofibrillary tangles) in the brains of affected individuals. Increasing evidence suggests that the formation of these deposits is closely associated with the age-related dysregulation of a large set of highly expressed and aggregation-prone proteins, which make up a metastable subproteome. To understand in more detail the origins of such dysregulation, we identify specific components of the protein homeostasis system associated with these metastable proteins by using a gene coexpression analysis. Our results reveal the particular importance of the protein trafficking and clearance mechanisms, including specific branches of the endosomal-lysosomal and ubiquitin-proteasome systems, in maintaining the homeostasis of the metastable subproteome associated with Alzheimer's disease.Alzheimer's disease | protein aggregation | protein homeostasis | supersaturation

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Protein homeostasis of a metastable subproteome associated with Alzheimer’s disease

Kundra

Ciryam

Morimoto

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Different approaches have been used to elucidate the molecular and cellular malfunctions that contribute to the disease pathogenesis in AD (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Among the tissues studied are neuronal tissue, skin fibroblasts, platelets, lymphocytes, and body fluids, such as plasma and cerebrospinal fluid (18).…”

mentioning

confidence: 99%

A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings

Nagasaka

Dillner

Ebise

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Alzheimer's disease (AD) is a neurodegenerative disease with an insidious onset and progressive course that inevitably leads to death. The current diagnostic tools do not allow for diagnosis until the disease has lead to irreversible brain damage. Genetic studies of autosomal dominant early onset familial AD has identified three causative genes: amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2). We performed a global gene expression analysis on fibroblasts from 33 individuals (both healthy and demented mutation carriers as well as wild-type siblings) from three families segregating the APP SWE, APPARC and PSEN1 H163Y mutations, respectively. The mutations cause hereditary progressive cognitive disorder, including typical autosomal dominant AD. Our data show that the mutation carriers share a common gene expression profile significantly different from that of their wildtype siblings. The results indicate that the disease process starts several decades before the onset of cognitive decline, suggesting that presymptomatic diagnosis of AD and other progressive cognitive disorders may be feasible in the near future.familial autosomal dominant mutations ͉ gene expression profiling ͉ human fibroblasts ͉ presymptomatic diagnosis ͉ DNA microarray

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“…In combination, studies such as these provide possible clues, regarding which gene systems, such as those involved in neurogenesis, to examine further in associational analyses. However, an important consideration is that many mRNA transcripts may change either with healthy aging or with other age-related disease processes (Lukiw, 2004;Ricciarelli et al, 2004;Toescu et al, 2004). Thus, it will be crucial to consider the aging process and associated disease processes in interpreting data specifically related to geriatric depression.…”

Section: Genetics Researchmentioning

confidence: 99%

Translational Research in Late-Life Mood Disorders: Implications for Future Intervention and Prevention Research

Smith

Gunning-Dixon

Lotrich

et al. 2007

Neuropsychopharmacol

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Clinical and epidemiological studies have consistently observed the heterogeneous symptomatology and course of geriatric depression. Given the importance of genetic and environmental risk factors, aging processes, neurodegenerative and cerebrovascular disease processes, and medical comorbidity, the integration of basic and clinical neuroscience research approaches is critical for the understanding of the variability in illness course, as well as the development of prevention and intervention strategies that are more effective. These considerations were the impetus for a workshop, sponsored by the Geriatrics Research Branch in the Division of Adult Translational Research and Treatment Development of the National Institute of Mental Health that was held on September 7-8, 2005. The primary goal of the workshop was to bring together investigators in geriatric psychiatry research with researchers in specific topic areas outside of geriatric mental health to identify priority areas to advance translational research in geriatric depression. As described in this report, the workshop focused on a discussion of the development and application of integrative approaches combining genetics and neuroimaging methods to understand such complex issues as treatment response variability, the role of medical comorbidity in depression, and the potential overlap between depression and dementia. Future directions for integrative research were identified. Understanding the nature of geriatric depression requires the application of translational research and interdisciplinary research approaches. Geriatric depression could serve as a model for translational research integrating basic and clinical neuroscience approaches that would have implications for the study of other neuropsychiatric disorders.

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Microarray Analysis in Alzheimer's Disease and Normal Aging

Cited by 82 publications

References 30 publications

Protein homeostasis of a metastable subproteome associated with Alzheimer’s disease

Protein homeostasis of a metastable subproteome associated with Alzheimer’s disease

A unique gene expression signature discriminates familial Alzheimer's disease mutation carriers from their wild-type siblings

Translational Research in Late-Life Mood Disorders: Implications for Future Intervention and Prevention Research

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