Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1

Background: In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms. Objective: To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation. Methods: We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases. Results: The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions. Conclusion: The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Ap species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age

Age-related dissociation of N400 effect and lexical priming

The use of contextual information is an important capability to facilitate language comprehension. This can be shown by studying behavioral and neurophysiological measures of accelerated word recognition when semantically or phonemically related information is provided in advance, resulting in accompanying attenuation of the respective event-related potential, i.e. the N400 effect. Against the background of age-dependent changes in a broad variety of lexical capacities, we aimed to study whether word priming is accomplished differently in elderly compared to young persons. 19 young (29.9 ± 5.6 years) and 15 older (69.0 ± 7.2 years) healthy adults participated in a primed lexical decision task that required the classification of target stimuli (words or pseudo-words) following related or unrelated prime words. We assessed reaction time, task accuracy and N400 responses. Acceleration of word recognition by semantic and phonemic priming was significant in both groups, but resulted in overall larger priming effects in the older participants. Compared with young adults, the older participants were slower and less accurate in responding to unrelated word-pairs. The expected N400 effect was smaller in older than young adults, particularly during phonemic word and pseudo-word priming, with a rather similar N400 amplitude reduction by semantic relatedness. The observed pattern of results is consistent with preserved or even enhanced lexical context sensitivity in older compared to young adults. This, however, appears to involve compensatory cognitive strategies with higher lexical processing costs during phonological processing in particular, suggested by a reduced N400 effect in the elderly

Sex-differences of face coding: evidence from larger right hemispheric M170 in men and dipole source modelling.

The processing of faces relies on a specialized neural system comprising bilateral cortical structures with a dominance of the right hemisphere. However, due to inconsistencies of earlier findings as well as more recent results such functional lateralization has become a topic of discussion. In particular, studies employing behavioural tasks and electrophysiological methods indicate a dominance of the right hemisphere during face perception only in men whereas women exhibit symmetric and bilateral face processing. The aim of this study was to further investigate such sex differences in hemispheric processing of personally familiar and opposite-sex faces using whole-head magnetoencephalography (MEG). We found a right-lateralized M170-component in occipito-temporal sensor clusters in men as opposed to a bilateral response in women. Furthermore, the same pattern was obtained in performing dipole localization and determining dipole strength in the M170-timewindow. These results suggest asymmetric involvement of face-responsive neural structures in men and allow to ascribe this asymmetry to the fusiform gyrus. This specifies findings from previous investigations employing event-related potentials (ERP) and LORETA reconstruction methods yielding rather extended bilateral activations showing left asymmetry in women and right lateralization in men. We discuss our finding of an asymmetric fusiform activation pattern in men in terms of holistic face processing during face evaluation and sex differences with regard to visual strategies in general and interest for opposite faces in special. Taken together the pattern of hemispheric specialization observed here yields new insights into sex differences in face perception and entails further questions about interactions between biological sex, psychological gender and influences that might be stimulus-driven or task dependent

Sex-difference in hemispheric organization during face processing: Magnetic activity in sensor-clusters over left and right hemisphere averaged across 13 female (red) and 13 male (blue) subjects.

<p>M170 amplitude is larger in the right hemisphere in men without laterality effects in female participants. Note that M170-amplitudes were inverted to make comparisons possible.</p