Liana Lisboa Fernandez

Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

BACKGROUND The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurrence of Alzheimers disease (AD) is still controversial. OBJECTIVE To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimers 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 analysis 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-dependent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.

Effects of Increased Iron Intake During the Neonatal Period on the Brain of Adult AβPP/PS1 Transgenic Mice

The present study was aimed to investigate neuropathological changes in AbetaPP/PS1 transgenic mice (Tg), as a model of Alzheimers disease, subjected to supplementary iron administration in a critical postnatal period, in order to reveal the interaction of genetic and environmental risk factors in the pathogenesis of the disease. Twelve Tg and 10 wild-type (Wt) littermates were administered iron between the 12th and 14th post-natal days (TgFe, WtFe); 11 Tg and 15 Wt received vehicle (sorbitol 5%) alone in the same period (TgSb, WtSb). Mice were killed at the age of six months and processed for morphological and biochemical studies. No modifications in amyloid-beta burden were seen in iron-treated and non-iron-treated AbetaPP/PS1 mice. No differences in microglial reactions were observed when comparing the four groups of mice. Yet increased astrocytosis, as revealed by densitometry of GFAP-immunoreactive astrocytes, and increased expression levels of GFAP, as revealed by gel electrophoresis and western blotting, were found in iron-treated mice (both Tg and Wt) when compared with TgSb and WtSb. This was accompanied by significant changes in brain fatty acid composition in AbetaPP/PS1 mice that led to a lower membrane peroxidizability index and to reduced protein oxidative damage, as revealed by reduced percentages of the oxidative stress markers: glutamic semialdehyde, aminoadipic semialdehyde, Nepsilon-carboxymethyl-lysine, Nepsilon-carboxyethyl-lysine, and Nepsilon-malondialdehyde-lysine. These findings demonstrate that transient dietary iron supplementation during the neonatal period is associated with cellular and metabolic imprinting in the brain in adult life, but it does not interfere with the appearance of amyloid plaques in AbetaPP/PS1 transgenic mice.

Um modelo de avaliação das funções corticais

The authors suggest a protocol elaborated to standardize the evaluation of high brain functions that should become an element for localization of cortical pathology.

FOXP2 Expression in Frontotemporal Lobar Degeneration-Tau

FOXP2 is altered in a variety of language disorders. We found reduced mRNA and protein expression of FOXP2 in frontal cortex area 8 in Picks disease, and frontotemporal lobar degeneration-tau linked to P301L mutation presenting with language impairment in comparison with age-matched controls and cases with parkinsonian variant progressive supranuclear palsy. Foxp2 mRNA and protein are also reduced with disease progression in the somatosensory cortex in transgenic mice bearing the P301S mutation in MAPT when compared with wild-type littermates. Our findings support the presence of FOXP2 expression abnormalities in sporadic and familial frontotemporal degeneration tauopathies.

Neuropathological Changes in Adult and Old Rats Following Early Post-Natal Iron Administration

acetylcholine esterase (AChE) activity. Evidence for cholinergic dysfunction in early stages of Alzheimer’s disease (AD) or mild cognitive impairment (MCI) is inconclusive, and human studies of the relationship of cholinergic function with neuropsychological performance in vivo are rare. Methods: We included 21 healthy controls, 20 MCI and 15 mild AD patients. A comprehensive neuropsychological battery was administered to indicate the general cognitive function and to define performance of verbal and non-verbal memory, language, executive function and visuoconstructive abilities. [11C]-MP4A PET was applied in all subjects, parametric images of tracer hydrolysis rate constant k3 were generated and analysed using standard atlas regions. After principal component analysis (PCA) of k3 values correlational analysis with neuropsychological test results was performed. Results: The mean global k3 values of MCI (0.076 6 0.011 min-1) and AD patients (0.066 6 0.009 min-1) were significantly lower than that of controls (0.084 6 0.006 min-1) (p < 0.05 and p < 0.001, respectively) with the temporal regions showing the strongest decline in both patient groups. PCA revealed three main components representing frontal and parietal regions (PC1), temporal regions (PC2) and hippocampus and amygdala (PC3). PC 2 could separate all three diagnostic groups. Significant correlations in the whole group between PC2 and neuropsychological performances were found, most strongly with impaired verbal and visual memory function as well as impaired working memory, but also with deficient visuo-spatial and executive functions. The association of verbal and non-verbal memory with the ‘‘temporal’’ PC 2 was confirmed in MCI patients. This is in line with neuropathological studies showing the greatest and most consistent loss of cholinergic neurons in AD in the posterior part of the nucleus basalis Meynert (nbM-Ch4p), which primarily sends cholinergic projections to the temporal cortex (Geula and Mesulam, 1999). Conclusions: Cholinergic dysfunction in the temporal lobe is an early hallmark in MCI and mild AD and it is associated with impaired neuropsychological function.

P1-302: MTHFR and APOE polymorphisms in a case-control study of Alzheimer’s disease

aging. This observation is consistent with the idea that the gradual downregulation of NEP expression, resulting in a corresponding elevation in the steady-state levels of A , over a decade or more, may cause A accumulation that triggers the AD pathological cascade. Additionally, higher mRNA levels of IDE and NEP were detected in the human cerebellum than in the frontal cortex, which may partly explain why cerebellum exhibits only minor plaque pathology. Conclusions: These data suggest that ageand region-specific changes in the proteolytic clearance of A make an important contribution to pathogenic mechanisms in AD.

Alterações encontradas em cérebros de indivíduos acima dos 65 anos e sua correlação com demência de Alzheimer

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 β-amyloid: -β -amyloid immunohistochemistry; Glees technique; and haematoxilin-eosin technique. We detected significant differences between the number of senile plaques found in different techniques. β-amyloid immunohistochemistry was more efficient. This is very important because we can underdiagnosis Alzheimers 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 β-amyloid importance was done.

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

The authors observed 24 children that are studying for the first time in the first grade of the elementary school. They were observed through the classical neurological examination, the evolutive neurological examination and through tests for evaluation of cortical functions. It is analyzed the school performance in report to the evolutive neurological performance and to the tests for cortical functions. Results obtained are compared and discussed. The authors conclude that the usage of these two evaluation instruments is able to discriminate the good from the bad school performance.