Objectives

To study depressive symptoms in preclinical presenilin-1 (PS1) related Alzheimer's disease.

Methods

Participants were 33 Mexican women at risk for inheriting PS1 mutations who were not demented. They were interviewed, underwent cognitive testing, and completed the Beck depression inventory (BDI). PS1 mutation status was determined. Mean BDI scores were compared between PS1 mutation carriers and non-carriers. The percentage of subjects who reported seeing a psychiatric professional, and the percentage complaining of memory loss were compared between groups. Regression analysis was used to determine whether mutation status predicted BDI scores after adjusting for age, education, mini-mental state examination, and subjective memory function.

Results

PS1 mutation carriers (n = 17) scored significantly higher than non-carriers (n = 16) on the BDI (mean score, 14.4 v 6.5, p = 0.017); 24% of mutation carriers and 12.5% of non-carriers admitted having sought help from a psychiatric professional (NS). Mutation status remained a significant predictor of BDI scores after adjusting for potential covariates. Though not demented, mutation carriers tended to score lower than non-carriers on several neuropsychological tests.

Conclusions

Depressive symptoms can occur early in the course of PS1 related Alzheimer's disease, at least in women. This supports the hypothesis that depression may occur as a direct result of the neuropathology underlying Alzheimer's disease.

OBJECTIVE: To determine if genetic status in persons at-risk for inheriting a Presenilin-1 (PS1) mutation influences level of educational attainment. BACKGROUND: There is convergent evidence suggesting that an increasing level of intellectual achievement protects one from manifesting the cognitive decline of Alzheimer’s disease (AD). These data however, being largely retrospective, are subject to many biases. Considering the dell described genetic contributions to the development of AD, another possible explanation for these associations is that people predisposed to develop AD have a life-long cognitive disadvantage that limits their educational attainment. We studied persons at-risk for the development of autosomal dominant AD to test this hypothesis. DESIGN/METHODS: Twenty-five persons representing 4 distinct Mexican families at-risk for inheriting a PS-1 mutation were enrolled in a study measuring demographic variables, rick factors, and score on neurocognitive tests. Subjects were not excluded if they had subjective memory complaints or cognitive decline had been noted by an informant but were excluded if they had experienced functional decline. Mutation status was determined in 16 of theses subjects. TO reduce cohort effects only subjects between the ages of 20 and 45 were considered. No subject was currently enrolled in school of had plans to continue schooling. Mutation carriers and non-mutation carriers were compared using an independent samples T-tests with regard to age, years or education, self-reported average grades, Mini-Mental State Examination (MMSE) scores, and Beck Depression Inventory (BDI) scores. RESULTS: Five carriers (3 female, 2 male) of the A431E mutation in PS1 were compared to 6 related non-carriers (all female). Subjects represented 3 superficially distinct families carrying this same mutation. Mean ages were 32 (range, 22-44) for carriers and 36 (range, 23-45) for non-carriers (non-significant, ns). Non-carriers had significantly more years of education than did carriers (16.3 vs. 11.4, p<.05) and had slightly better mean self-reported grades (8.5 vs. 7.6 on a scale from 1-10 ns). Mean MMSE scores did not differ between the groups (28.3 in non-carriers, 28.6 in carriers). Mean self-rated depression as measured on the Beck Depression Inventory was higher for the mutation carriers (18.8) than for the non-carriers (5.5) though this difference was not statistically significant (p=.06). CONCLUSIONS: Despite having grossly comparable cognitive function, carries of a PS1 mutation causing autosomal dominant AD did not achieve as high a level of education as did their non-mutation carrying kin. This is consistent with the hypothesis that persons predisposed to develop AD may have subtle, possibly life-long, cognitive deficits which limit their intellectual achievement. Further study of this group with more rigorous control of other psychological, psychiatric, and socioeconomic variables should help to evaluate the contribution of other factors including educational attainment in this population. Supported by: Alzheimer’s Association Grant NIRG-01-2797 Disclosure: John M. Ringman has nothing to disclose.

Background

Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD).

Objective

To investigate these observations by the study of persons at risk for autosomal dominant forms of AD.

Methods

Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE epsilon4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs.

Results

MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE epsilon4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores.

Conclusions

This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE epsilon4 allele did not demonstrate large influences on neuropsychological performance.

Methyloferula stellata AR4 is an aerobic acidophilic methanotroph, which, in contrast to most known methanotrophs but similar to Methylocella spp., possesses only a soluble methane monooxygenase. However, it differs from Methylocella spp. by its inability to grow on multicarbon substrates. Here, we report the draft genome sequence of this bacterium.

The genomes of the aerobic methanotrophs "Methyloterricola oryzae" strain 73aT and Methylomagnum ishizawai strain 175 were sequenced. Both strains were isolated from rice plants. Methyloterricola oryzae strain 73aT represents the first isolate of rice paddy cluster I, and strain 175 is the second representative of the recently described genus Methylomagnum.

The genome sequences of Methylobacter marinus A45, Methylobacter sp. strain BBA5.1, and Methylomarinum vadi IT-4 were obtained. These aerobic methanotrophs are typical members of coastal and hydrothermal vent marine ecosystems.