The Genetics of Alzheimer’s Disease in Brazil: 10 Years of Analysis in a Unique Population

Oliveira, João Ricardo Mendes de; Nishimura, Agnes L.; Lemos, R. R.; Zatz, Mayana

doi:10.1007/s12031-008-9124-0

Cited by 13 publications

(5 citation statements)

References 35 publications

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“…Thus, it is important to improve our knowledge about the genetic aspects of AD through studies of different Brazilian cities. Compared to other studies, our sample size was one of the largest analyzed thus far in Brazil for APOE polymorphisms (15,17,21,30). …”

Section: Discussionmentioning

confidence: 99%

Protective effect of the APOE-e3 allele in Alzheimer’s disease

de-Almada

de-Almeida

Camporez

et al. 2012

Braz J Med Biol Res

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Although several alleles of susceptibility to Alzheimer's disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95%CI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95%CI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to estabilish a profile of risk for AD in the population from Vitória, ES.

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Section: Discussionmentioning

confidence: 99%

Protective effect of the APOE-e3 allele in Alzheimer’s disease

de-Almada

de-Almeida

Camporez

et al. 2012

Braz J Med Biol Res

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“…New discoveries of risk genes with small [57] and large populations suggest multifactorial influences which culminate in NFT formation and neuronal cell death [58].…”

Section: Tau and Cognitive Impairmentmentioning

confidence: 99%

Tau Pathology and Future Therapeutics

Gozes

2010

CAR

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The current review discusses microtubules and tau in the healthy brain and move on to the underling pathology of Alzheimer's disease (AD) with emphasis on tau and neurofibrillary tangles. Tangles have been associated with cognitive dysfunction causing neurodegeneration in the absence of plaques. AD, the most abundant tauopathy is characterized by β-amyloid plaques and tau tangles. An abundance of tau inclusions, in the absence of β-amyloid deposits, defines Pick's disease (frontotemporal lobar degeneration), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and other diseases. Our own focused research is on activity-dependent neuroprtective protein (ADNP). Our findings show that ADNP-deficiency leads to tauopathy which is inhibited by the ADNP derived drug candidate, davunetide (originally known as NAP). The current review further describes tau as a potential diagnostic marker followed by drug candidates that are aimed at fighting tau pathology. A recent historical perspective is the final comment of the manuscript. This paper is not a comprehensive review of the literature rather it gives my own point of view in the face of many publications and a great unmet need for future therapeutics. It is hoped that davunetide, a most advanced drug in clinical development will rapidly advance as a first effective treatment for a number of brain disorders broadly categorized as frontotemporal dementia (FTD) and serve as a prototype for future therapeutic development toward modification and remedy of currently intractable neurodegenerative diseases.

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“…Motivated by the previous interest of our group in genetic polymorphisms of the Interleukin-1 panel in AD and Mood Disorders, we selected genes from an expression microarray study in hippocampus of affected patients which infers that the up-regulation of IL-1α, IL-1β, COX-2, PLA2G4A, and CD83 genes could be due to the inflammatory process, neurotoxicity and cell death (Colangelo et al 2002;Fertuzinhos et al 2004;Oliveira et al 2009). …”

Section: Introductionmentioning

confidence: 99%

In Silico Identification of New Genetic Variations as Potential Risk Factors for Alzheimer’s Disease in a Microarray-oriented Simulation

et al. 2009

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Genomic and proteomic studies of neurodegenerative disorders require complementary approaches to integrate the massive amount of data generated in high throughput experimental procedures. We propose a Bioinformatics pipeline in which expression studies guide the selection of candidate genes that should be screened for potential new genetic variations from a public expressed site tags (ESTs) database. Motivated by the former interest of our group in genetic polymorphisms involved with the immune system, we selected five genes from a previous expression microarrays study of hippocampal cornu ammonis (CA1) area of Alzheimer's Disease subjects (AD). The CLCbio Workbench Combined version 3.6.2. was initially used to build ESTs and mRNA files retrieved respectively from the Goldenpath of University of California Santa Cruz (UCSC) and National Center for Biotechnology Information (NCBI) databases and latter to perform multiple batches of Smith-Waterman alignments. A total of 116 ESTs sequences were selected after proper stringent parameters were applied to the first set of mismatches. The annotation revealed various classes of variations, most of them deletions (176). Amongst this specific group, some were frameshift deletions (35) and the virtual translation of a few others (5) were predicted to induce no change other than a single aminoacid removal, with no subsequent repercussions at the protein sequence. In addition, the analysis identified transitions (three), transversions (52), synonymous (41), non-synonymous (12), and deletions in 36 ESTs located in Untranslated Regions -UTRs (Supplementary data). Deletions are often associated to major genetics syndromes with dysmorphic features. However, various recent studies show that common microdeletions might be highly associated with common neuropsychiatric disorders such as schizophrenia, autism, mental retardation, or even in various ethnicities, detected in whole genome sequencing experiments. A virtual validation confirmed that some of the variations identified were previously reported and confirmed in DNA samples, showing that this method is a feasible way to detect genetic variations that merit further exploration in AD genetic risk factor association studies.

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The Genetics of Alzheimer’s Disease in Brazil: 10 Years of Analysis in a Unique Population

Cited by 13 publications

References 35 publications

Protective effect of the APOE-e3 allele in Alzheimer’s disease

Protective effect of the APOE-e3 allele in Alzheimer’s disease

Tau Pathology and Future Therapeutics

In Silico Identification of New Genetic Variations as Potential Risk Factors for Alzheimer’s Disease in a Microarray-oriented Simulation

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