Genetics of Dementia (original) (raw)

Genetics and dementia: Risk factors, diagnosis, and management

Alzheimer's & Dementia, 2007

New developments in molecular genetics have improved our understanding on a number of neurodegenerative dementias considerably, especially Alzheimer's disease and frontotemporal dementia. However, this explosion of information can be overwhelming to clinicians, making it difficult to integrate into regular clinical practice. In this article, we briefly reviewed our current understanding regarding causative genetic mutations and genetic risk factors on the major forms of dementia, which provided the background information for discussion in the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. The principles of genetic counselling were applied. Guidelines and recommendations on the application of genetics in the assessment, diagnosis, and management of patients and families with dementia were summarized.

Genetic factors in Alzheimer's disease: A review of recent advances

Annals of Neurology, 1996

Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly [I]. It is a clinical-pathological entity that includes progressive dementia associated with the neuropathological hallmarks of AP amyloid plaques, neurofibrillary tangles (NFTs), and amyloid angiopathy. The prevalence of AD is age dependent, and has been estimated to double every 5 years beyond age 65: from 1 to 4% at age 65 to 70 years to 22% or higher at ages 85 to 90 years [2]. High prevalence andllate age at onset are features usually considered uncharacteristic of a genetic disease, but in the past 5 years, the identification of genes that cause or modulate AD has clearly demonstrated that AD can have a genetic basis. In this review, we discuss the current knowledge of the genetics of AD.

Genetic risk factors in Alzheimer's disease

Molecular Pathology, 1998

Following a brief introduction and discussion of the pathological features of Alzheimer's disease, the main emphasis of this review article will be the genetic factors that have been implicated in this disease. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial Alzheimer's disease will be discussed. These are well characterised but account for only a small proportion of Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease. Many of these are controversial and studies have shown conflicting results, which are discussed in this section. Finally, a brief discussion of some of the mechanisms suggested to play a role in the pathogenesis of Alzheimer's disease is included. It is hoped that this will show why particular genes have been implicated in Alzheimer's disease and how they might be able to influence the development of the disease. (J Clin Pathol: Mol Pathol 1998;51:293-304)

Genetic risk factors of Alzheimer’s disease

European Journal of Clinical and Experimental Medicine

Introduction. Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, which is a serious health problem for societies that live longer. Spontaneous dominant mutations and polymorphisms of selected genes play an important role in development of AD. Aim. Several polymorphisms in selected genes strongly associated with development of Alzheimer's disease were highlighted in this review: APOE, CYP46, APP, PSEN1, PSEN2, UBQLN1, BACE1, PRND, APBB2, TOMM 40. These gene polymorphisms have a significant role in the development of Alzheimer's disease and they have potential to be biomarkers. Researchers combine efforts to find significant polymorphisms that would ensure that a person is predisposed to the occurrence of disease symptoms. This topic is often taken up by scientists seeking to develop effective genetic tests for diagnosing AD. Material and methods. Analysis of literature from web of knowledge: Web of Science (all database), NCBI and PubMed. Results. We reviewed the selected important genes and polymorphisms which are most often associated with development of AD. Conclusion. It should be noted that nowadays scientists strive not to focus on only one polymorphism in the gene but on several polymorphisms in different genes concomitantly and above all on interactions between them to the diagnosis of this disease. Only this approach to AD will contribute to the creation of appropriate identification methods. Moreover, we should use the new generation tools-the platform for collecting data and personalized medicine.

Genetics of Alzheimer's Disease. A Rapidly Evolving Field

Journal of Alzheimer's Disease, 2007

Genetic factors have a variable impact on Alzheimer's Disease (AD), ranging from familial forms that are transmitted in an autosomal dominant fashion to sporadic AD, where a polygenic component is present. Most genes conferring susceptibility to AD are related to amyloid-β deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) and inflammatory response (IL-1 α; IL-1 β; IL-6; TNF-α). Genome-wide analyses, transcriptomics and proteomics approaches have pointed also to proapoptotic genes as increasing AD liability. Depression and psychotic symptoms that occur in a large proportion of AD patients have been associated with monoamine genes coding for metabolic enzymes (COMT), transporters (5-HTTLPR) and receptors (DRD1; DRD3). Genetic testing may be useful to confirm the diagnosis of AD in individuals with clinical signs of dementia, while it is generally not recommended as a predictive testing for AD in asymptomatic individuals. Drugs currently in use to treat AD are effective in only 20% of patients; their therapeutic effect is predominantly under genetic control (CYP26 gene; APOE). Environmental factors have been shown to moderate the effects of genes on psychiatric disorders such as depression, schizophrenia and ADHD. The study of gene-environment interactions in AD, that are still poorly understood, is essential to predict disease-risk in asymptomatic individuals. Genomics will provide a dynamic picture of biological processes in AD and new targets for the forthcoming anti-AD drugs.

Genetic of Alzheimer's Disease: A Narrative Review Article

Iranian journal of public health, 2015

Alzheimer's disease (AD) is one of the most common problems for old peoples. Etiology of AD is not clear, but genetic factors play a major role in determining a person's risk to develop AD. Twin and family studies confirm that AD has a genetic basis. AD genetics has been split into two broad categories: early-onset and late-onset. EOAD cases are inherited in an autosomal dominant pattern. In this form, dominant mutations in genes like APP, PSEN-1 and PSEN-2 associated with AD. This study aimed to consider the role of genetic in AD. At the first, most of the references in relation with genetic basis of AD searched from the following web-sites: PubMed, Science direct, Wiley & Sons (1995-2014). Then, the most common genes and their affects described briefly. Aging is the most obvious risk factor for developing AD. There is a genetic basis for AD, of course this relation is not complete but it is significant. More than thousand genes studied in relation with Alzheimer's dise...

Genetic factors associated with the predisposition to late onset Alzheimer's disease

Gene, 2019

Background: Alzheimer disease is a progressive, irreversible neurodegenerative disorder characterized by loss of memory and cognitive skills. More than 90% of cases are sporadic and have later age of onset. Many studies have shown a genetic predisposition for late onset Alzheimer disease (LOAD). The most studied genetic predisposition factor is apolipoprotein E gene besides other susceptibility genes involved in vascular pathologies, homocysteine metabolism, and neuronal growth and differentiation such as methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), APOB and brain derived neurotrophic factor (BDNF). Methods: In this study Factor V Leiden (G1691A) and H1299R, prothrombin G20210A, Factor XIII V34L, B-fibrinogen-455G>A, PAI-1 5G/4G, HPA1 b/a, MTHFR C677T, MTHFR A1298C, APOE, ACE I/D, BDNF C270T and G196A polymorphisms were evaluated in 100 LOAD patients and 100 age matched healthy controls. Results: APOE4 allele, MTHFR CC A1298C and BDNF TT C270T genotypes were significantly higher in LOAD patients compared to the control group (p<0.001, p=0.04, p=0.03, respectively). There were no significant associations between other genotypes and allele frequencies. Mini-Mental State Examination (MMSE) scores and age at onset of the patients were also evaluated for each and combined genotypes. Age at onset was significantly lowered by about approximately 4 and 5 years in patients carrying BDNF TT C270T and MTHFR TT C677T genotypes, respectively. Conclusion: APOE, MTHFR A1298C and BDNF C270T polymorphisms may be associated with LOAD and BDNF and MTHFR alleles may play a role in the age at onset of the LOAD.