Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE? Polimorfismo da MTHFR é um fator de risco para demência de Alzheimer como APOE?

BACKGROUND: The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurence of Alzheimer's disease (AD) is still controversial: OBJECTIVE: To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimer's disease. METHOD: This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated anlysis adjust by Mantel-Haenszel method. RESULTS: There was significant difference about APOE4 and APOE2 in the groups. (p=0.002) The odds ratio increased exponentially with the increased number of E4 allele (chi2 linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups. CONCLUSION: The APOE4 is a risk factor and demonstrated a dose-depenent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.<br>INTRODUÇÃO: O papel do polimorfismo do gene da metilenotetrahidrofolato redutase (MTHFR) como um fator de risco para demência de Alzheimer (DA) é controverso ainda. OBJETIVO: Verificar a associação entre os polimorfismos da MTHFR e apolipoproteína E (APOE) e DA. MÉTODO: O trabalho foi conduzido como um estudo caso-controle. Trinta pacientes com DA provável foram incluídos no grupo caso. Vinte e nove indivíduos sem demência comprovadas por testes neuropsicológicos, emparelhados pela idade, sexo, cor e nível educacional constituíram o grupo controle. DNA foi isolado de leucócitos periféricos extraídos de sangue venoso anticoagulado. Genótipos de APOE e MTHFR foram realizados por amplificação de DNA e digestão. As freqüências dos genótipos da APOE e MTHFR foram submetidas ao teste do chi-quadrado corrigido pelo teste de Fisher; os genótipos da APOE, ao teste do chi-quadrado com tendência linear e as freqüências da MTHFR mutante e DA à análise estratificada corrigida pelo método de Mantel-Haenszel. RESULTADOS: Houve diferença significativa entre APOE4 e APOE2 nos grupos (p=0,002). O odds ratio aumentou exponencialmente com o aumento do número de alelo E4 (teste chi2 com tendência linear). Nenhuma diferença significativa foi detectada nos genótipos da MTHFR em ambos grupos caso e controle. CONCLUSÃO: O alelo APOE4 é um fator de risco e demonstrou efeito dose-dependente enquanto o alelo E2 conferiu proteção para DA. A mutação da MTHFR não teve correlação dom DA

Alterações encontradas em cérebros de indivíduos acima dos 65 anos e sua correlação com demência de Alzheimer Changes found in the brain of people over 65 years old and their correlation with Alzheimer disease

Foram estudadas 12 amostras de cérebros de indivíduos acima de 65 anos. Estas amostras foram submetidas a três técnicas com o objetivo de se detectar placas senis ricas em &#946;-amilóide: imuno-histoquímica para &#946;-amilóide; técnica de Glees; técnica da hematoxilina-eosina. Foram detectadas diferenças significativas entre o número de placas encontradas nas diferentes técnicas, o que salienta a possibilidade de diagnósticos falsos-negativos na doença de Alzheimer. A técnica de imuno-histoquímica mostrou-se mais eficiente. Foram submetidos a teste estatístico o número de placas encontradas no cortex e no hipocampo e comparadas, assim como o número de placas encontradas num hemisfério e no outro, sem diferenças significativas. Segue-se revisão da literatura quanto aos achados neuropatológicos da doença de Alzheimer, assim como da significância do &#946;-amilóide.Twelve brains of individuals with more than sixty-five years were studied. These samples were submitted to three techniques, with the objective to detect senile plaques which the major component was the &#946;-amyloid: -&#946; -amyloid immunohistochemistry; Glees technique; and haematoxilin-eosin technique. We detected significant differences between the number of senile plaques found in different techniques. &#946;-amyloid immunohistochemistry was more efficient. This is very important because we can underdiagnosis Alzheimer's disease when the most adequate technique is not used. The statistical analysis showed no significant differences neither between the number of cortical plaques and the hipocampal plaques,nor between the number of plaques in both hemispheres. A literature review about neuropathological findings and &#946;-amyloid importance was done

Avaliação neurológica evolutiva e das funções corticais numa amostra de crianças da primeira série

Os autores estudam 24 crianças que cursam pela primeira vez a primeira série do primeiro grau, mediante o exame neurológico clássico, bem como do exame neurológico evolutivo e de provas para avaliar funções corticais. Analisam o desempenho escolar em relação ao desempenho no exame neurológico evolutivo e no exame das funções corticais. Comparam e discutem os resultados. Concluem que o uso desses dois instrumentos é capaz de discriminar o bom e o mau desempenho escolar

Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil

ABSTRACT Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43) and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG): 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP). Of the patients in the non-demented group (NDG), 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%). Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia

Diagnosis of Alzheimer's disease in Brazil: Supplementary exams

Abstract This article presents a review of the recommendations on supplementary exams employed for the clinical diagnosis of Alzheimer's disease (AD) in Brazil published in 2005. A systematic assessment of the consensus reached in other countries, and of articles on AD diagnosis in Brazil available on the PUBMED and LILACS medical databases, was carried out. Recommended laboratory exams included complete blood count, serum creatinine, thyroid stimulating hormone (TSH), albumin, hepatic enzymes, Vitamin B12, folic acid, calcium, serological reactions for syphilis and serology for HIV in patients aged younger than 60 years with atypical clinical signs or suggestive symptoms. Structural neuroimaging, computed tomography or - preferably - magnetic resonance exams, are indicated for diagnostic investigation of dementia syndrome to rule out secondary etiologies. Functional neuroimaging exams (SPECT and PET), when available, increase diagnostic reliability and assist in the differential diagnosis of other types of dementia. The cerebrospinal fluid exam is indicated in cases of pre-senile onset dementia with atypical clinical presentation or course, for communicant hydrocephaly, and suspected inflammatory, infectious or prion disease of the central nervous system. Routine electroencephalograms aid the differential diagnosis of dementia syndrome with other conditions which impair cognitive functioning. Genotyping of apolipoprotein E or other susceptibility polymorphisms is not recommended for diagnostic purposes or for assessing the risk of developing the disease. Biomarkers related to the molecular alterations in AD are largely limited to use exclusively in research protocols, but when available can contribute to improving the accuracy of diagnosis of the disease