Genome research in pre-dementia stages of Alzheimer's disease. 2016

Sonia Moreno-Grau, and Agustín Ruiz
Memory Clinic of Fundació ACE,Institut Català de Neurociències Aplicades,Barcelona,Spain.

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome, APOE is confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealed APOE as genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587-2.153); P = 2.80  × 10-15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015-1.304); P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration.

UI MeSH Term Description Entries
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003704 Dementia An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. Senile Paranoid Dementia,Amentia,Familial Dementia,Amentias,Dementia, Familial,Dementias,Dementias, Familial,Dementias, Senile Paranoid,Familial Dementias,Paranoid Dementia, Senile,Paranoid Dementias, Senile,Senile Paranoid Dementias
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D056726 Genetic Association Studies The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease. Candidate Gene Identification,Candidate Gene Analysis,Candidate Gene Association Studies,Candidate Gene Association Study,Gene Discovery,Genotype-Phenotype Association,Genotype-Phenotype Associations,Genotype-Phenotype Correlation,Genotype-Phenotype Correlations,Analyses, Candidate Gene,Analysis, Candidate Gene,Association Studies, Genetic,Association Study, Genetic,Association, Genotype-Phenotype,Associations, Genotype-Phenotype,Candidate Gene Analyses,Correlation, Genotype-Phenotype,Correlations, Genotype-Phenotype,Discovery, Gene,Gene Analyses, Candidate,Gene Analysis, Candidate,Gene Identification, Candidate,Genetic Association Study,Genotype Phenotype Association,Genotype Phenotype Associations,Genotype Phenotype Correlation,Genotype Phenotype Correlations,Identification, Candidate Gene,Studies, Genetic Association,Study, Genetic Association
D060825 Cognitive Dysfunction Diminished or impaired mental and/or intellectual function. Cognitive Disorder,Mild Cognitive Impairment,Cognitive Decline,Cognitive Impairments,Mental Deterioration,Cognitive Declines,Cognitive Disorders,Cognitive Dysfunctions,Cognitive Impairment,Cognitive Impairment, Mild,Cognitive Impairments, Mild,Decline, Cognitive,Declines, Cognitive,Deterioration, Mental,Deteriorations, Mental,Disorder, Cognitive,Disorders, Cognitive,Dysfunction, Cognitive,Dysfunctions, Cognitive,Impairment, Cognitive,Impairment, Mild Cognitive,Impairments, Cognitive,Impairments, Mild Cognitive,Mental Deteriorations,Mild Cognitive Impairments
D020022 Genetic Predisposition to Disease A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. Genetic Predisposition,Genetic Susceptibility,Predisposition, Genetic,Susceptibility, Genetic,Genetic Predispositions,Genetic Susceptibilities,Predispositions, Genetic,Susceptibilities, Genetic

Related Publications

Sonia Moreno-Grau, and Agustín Ruiz
September 2011, Alzheimer's research & therapy,
Sonia Moreno-Grau, and Agustín Ruiz
March 2024, The New England journal of medicine,
Sonia Moreno-Grau, and Agustín Ruiz
November 2005, Current opinion in psychiatry,
Sonia Moreno-Grau, and Agustín Ruiz
September 1999, Lancet (London, England),
Sonia Moreno-Grau, and Agustín Ruiz
January 2016, The journal of prevention of Alzheimer's disease,
Sonia Moreno-Grau, and Agustín Ruiz
February 1994, The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses,
Sonia Moreno-Grau, and Agustín Ruiz
April 2010, The journal of nutrition, health & aging,
Sonia Moreno-Grau, and Agustín Ruiz
January 2021, Journal of Alzheimer's disease : JAD,
Copied contents to your clipboard!