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Protein & Cell Feb 2017Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's... (Review)
Review
Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's disease, which makes most of cases. New researches indicate that gastrointestinal tract microbiota are directly linked to dementia pathogenesis through triggering metabolic diseases and low-grade inflammation progress. A novel strategy is proposed for the management of these disorders and as an adjuvant for psychiatric treatment of dementia and other related diseases through modulation of the microbiota (e.g. with the use of probiotics).
Topics: Alzheimer Disease; Gastrointestinal Microbiome; Humans
PubMed: 27866330
DOI: 10.1007/s13238-016-0338-6 -
Biological Psychiatry Feb 2018Alzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder caused by fully penetrant single gene mutations in a minority of cases, while the... (Review)
Review
Alzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder caused by fully penetrant single gene mutations in a minority of cases, while the majority of cases are sporadic or show modest familial clustering. These cases are of late onset and likely result from the interaction of many genes and the environment. More than 30 loci have been implicated in AD by a combination of linkage, genome-wide association, and whole genome/exome sequencing. We have learned from these studies that perturbations in endolysosomal, lipid metabolism, and immune response pathways substantially contribute to sporadic AD pathogenesis. We review here current knowledge about functions of AD susceptibility genes, highlighting cells of the myeloid lineage as drivers of at least part of the genetic component in late-onset AD. Although targeted resequencing utilized for the identification of causal variants has discovered coding mutations in some AD-associated genes, a lot of risk variants lie in noncoding regions. Here we discuss the use of functional genomics approaches that integrate transcriptomic, epigenetic, and endophenotype traits with systems biology to annotate genetic variants, and to facilitate discovery of AD risk genes. Further validation in cell culture and mouse models will be necessary to establish causality for these genes. This knowledge will allow mechanism-based design of novel therapeutic interventions in AD and promises coherent implementation of treatment in a personalized manner.
Topics: Alzheimer Disease; Animals; Genome-Wide Association Study; Humans
PubMed: 28666525
DOI: 10.1016/j.biopsych.2017.05.014 -
Nature Reviews. Neurology May 2022Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are... (Review)
Review
Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are more likely than older white individuals to have Alzheimer disease and related dementias. In this Perspective, we leverage our experience and expertise with older US Latino groups to review and discuss the need to integrate cultural factors into dementia research and care. We examine the importance of considering the effects of cultural factors on clinical presentation and diagnosis, dementia risk, clinical research and recruitment, and caregiving practices, with a focus on minoritized groups in the USA. We highlight critical gaps in the literature to stimulate future research aimed at improving the prevention and early detection of Alzheimer disease and related dementias and developing novel treatments and interventions across ethnoracially diverse populations. In addition, we briefly discuss some of our own initiatives to promote research and clinical care among Latino populations living in the USA.
Topics: Alzheimer Disease; Hispanic or Latino; Humans
PubMed: 35260817
DOI: 10.1038/s41582-022-00630-z -
Journal of Neurology, Neurosurgery, and... Jun 2002The four major degenerative dementias that often begin in presenescence: are reviewed. These are Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies,... (Review)
Review
The four major degenerative dementias that often begin in presenescence: are reviewed. These are Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, and Creutzfeldt-Jakob disease. Their epidemiological, genetic, and clinical features are reviewed, and controversies in taxonomy arising from recent discoveries described. Particular attention is given to the pathological role of protein aggregation, which appears to be a factor in each disease.
Topics: Aged; Alzheimer Disease; Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Incidence
PubMed: 12023408
DOI: 10.1136/jnnp.72.6.691 -
Translational Neurodegeneration Jan 2024Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that... (Review)
Review
Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.
Topics: Animals; Humans; Alzheimer Disease; Amyloid beta-Peptides; Aging; Brain; Memory Disorders
PubMed: 38254235
DOI: 10.1186/s40035-024-00397-x -
Journal of Alzheimer's Disease : JAD 2020As the most common form of senile dementia, Alzheimer's disease (AD) is accompanied by a great deal of uncertainty which can lead to fear and stigma for those identified... (Review)
Review
As the most common form of senile dementia, Alzheimer's disease (AD) is accompanied by a great deal of uncertainty which can lead to fear and stigma for those identified with this devastating disease. As the AD definition evolves from a syndromal to a biological construct, and early diagnoses becomes more commonplace, more confusion and stigma may result. We conducted a narrative review of the literature on AD stigma to consolidate information on this body of research. From the perspective of several stigma theories, we identified relevant studies to inform our understanding of the way in which implementation of the new framework for a biological based AD diagnosis may have resulted in new and emerging stigma. Herein, we discuss the emergence of new AD stigma as our understanding of the definition of the disease changes. We further propose recommendations for future research to reduce the stigma associated with AD.
Topics: Alzheimer Disease; Caregiver Burden; Cost of Illness; Early Diagnosis; Humans; Social Stigma
PubMed: 33044185
DOI: 10.3233/JAD-200932 -
British Journal of Pharmacology Sep 2019This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this...
This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.
Topics: Alzheimer Disease; Dementia; Humans; Precision Medicine
PubMed: 31468515
DOI: 10.1111/bph.14767 -
Health Affairs (Project Hope) Apr 2014Alzheimer's disease confronts us with an ethical challenge: How do we live with dignity and quality of life in the face of progressive disability and, ultimately, death?... (Review)
Review
Alzheimer's disease confronts us with an ethical challenge: How do we live with dignity and quality of life in the face of progressive disability and, ultimately, death? Patients' cognitive and decision-making impairments often make them unable to answer this question, and when professionals who provide services for older adults fail to recognize and accommodate these impairments, patients suffer. Patients and their caregivers need a health care system that fosters caregiving so that each will live with dignity and well-being. Another way to answer this question is to discover treatments that prevent disabling cognitive impairments, but this strategy will require expanding the Alzheimer's label to include people who do not have dementia or who are even cognitively normal. Controversies are likely to occur over how best to describe the Alzheimer's problem, measure the value of early diagnosis and treatment, and live with a brain at risk.
Topics: Aged; Alzheimer Disease; Caregivers; Cost of Illness; Delivery of Health Care; Humans; Mental Competency; Risk Factors
PubMed: 24711312
DOI: 10.1377/hlthaff.2014.0089 -
Journal of Alzheimer's Disease : JAD 2018Alzheimer's disease (AD) and frontotemporal dementia (FTD) represent the first cause of dementia in senile and pre-senile population, respectively. A percentage of cases... (Review)
Review
Alzheimer's disease (AD) and frontotemporal dementia (FTD) represent the first cause of dementia in senile and pre-senile population, respectively. A percentage of cases have a genetic cause, inherited with an autosomal dominant pattern of transmission. The majority of cases, however, derive from complex interactions between a number of genetic and environmental factors. Gene variants may act as risk or protective factors. Their combination with a variety of environmental exposures may result in increased susceptibility to these diseases or may influence their course. The scenario is even more complicated considering the effect of epigenetics, which encompasses mechanisms able to alter the expression of genes without altering the DNA sequence. In this review, an overview of the current genetic and epigenetic progresses in AD and FTD will be provided, with particular focus on 1) causative genes, 2) genetic risk factors and disease modifiers, and 3) epigenetics, including methylation, non-coding RNAs and chromatin remodeling.
Topics: Alzheimer Disease; Animals; Epigenesis, Genetic; Frontotemporal Dementia; Genetic Predisposition to Disease; Humans
PubMed: 29562532
DOI: 10.3233/JAD-170702 -
Genes Nov 2021Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ)...
Alzheimer's disease is a complex and multifactorial condition regulated by both genetics and lifestyle, which ultimately results in the accumulation of β-amyloid (Aβ) and tau proteins in the brain, loss of gray matter, and neuronal death [...].
Topics: Alzheimer Disease; Animals; Humans
PubMed: 34828400
DOI: 10.3390/genes12111794