750 research outputs found
Estrogen use and early onset Alzheimer's disease: a population-based study
Estrogen use may be protective for Alzheimer's disease with late onset.
However, the effects on early onset Alzheimer's disease are unclear. This
issue was studied in a population based setting. For each female patient,
a female control was matched on age (within 5 years) and place of
residence. Information on estrogen use and other risk factors were, for
cases (n=109) and controls (n=119), collected from the next of kin by
structured interview. The strength of the association between estrogen use
and early onset Alzheimer's disease was studied using conditional logistic
regression with adjustment for age and education level. There was an
inverse association between estrogen use and early onset Alzheimer's
disease (adjusted odds ratio 0.34; 95% confidence interval 0.12-0.94). The
study therefore suggests that estrogen use is beneficial to Alzheimer's
disease with early onset
APOE and the risk of PD with or without dementia in a population-based study.
OBJECTIVE: To study the association between APOE genotype and PD with or without dementia. METHODS: The study formed part of the Rotterdam Study, a prospective, population-based cohort study on the frequency, etiology, and prognosis of chronic diseases. The cohort examined for PD consisted of 6,969 independently living or institutionalized i
Absence of pathogenic mutations in presenilin homologue 2 in a conclusively 17-linked tau-negative dementia family
Characterization of an FTLD-PDB family with the coexistence of SQSTM1 mutation and hexanucleotide (G4C2) repeat expansion in C9orf72 gene
The C9orf72 expansion is considered a major genetic cause of familial frontotemporal dementia (FTD) in several patients' cohorts. Interestingly, C9orf72 expansion carriers, present also abundant neuronal p62-positive inclusions. Although p62/SQSTM1 mutations were initially associated with Paget disease of bone (PDB), they have been also identified in FTD. We describe an FTD-PDB family in which the proband presented with behavioral FTD phenotype and concomitant Paget disease. The molecular genetic analysis revealed the co-occurrence of 2 mutations; the pathogenic C9orf72 expansion and p.P392L heterozygous missense mutation in SQSTM1 gene. Amongst the 6 family members analyzed, the p.P392L SQSTM1 mutation segregated as expected with PDB, whereas the C9orf72 expansion segregated with frontal cognitive impairment or dementia in all but one carrier. The coexistence of these conditions could be underestimated since neither patients with FTD nor patients with PDB undergo bone scintigraphy or cognitive assessment, respectively. The number of cases with double mutations could also be over looked as the molecular strategy adopted in most laboratories ends with the identification of one pathogenic mutation in one of the known causative genes. Therefore, we advocate for further clinical and molecular evaluation in suspect cases
Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-Gly mutation
Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia
Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692 Ala => Gly mutation
Mutations at codons 717 and 670/671 in the amyloid precursor protein (APP) are rare genetic causes of familial Alzheimer's disease (AD). A mutation at codon 693 of APP has also been described as the genetic defect in hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). We have reported a APP692Ala-->Gly (Flemish) mutation as a cause of intracerebral hemorrhage and presenile dementia diagnosed as probable AD in a Dutch family. We now describe the post-mortem examination of two demented patients with the APP692 mutation. The neuropathological findings support the diagnosis of AD. Leptomeningial and parenchymal vessels showed extensive deposition of A
Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE {varepsilon}4 carriers (age range: 49–74 years; 19 females), of which 10 were homozygous for the {varepsilon}4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE {varepsilon}4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE {varepsilon}4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level
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