[Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus]. / Familiäre Alzheimer-Variante mit Amyloidangiopathie als Ausdruck einer APP-Gen-Duplikation.

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

Temporal modeling demonstrates preserved overlearning processes in schizophrenia: an fMRI study.

Working memory (WM) deficits are a core feature of schizophrenia. However, it has not been examined whether these deficits are related to altered temporal dynamics of information acquisition and changes in executive cognitive control. Therefore, the present study intended to quantify and model the dynamic process of information acquisition during continuous overlearning of WM information. It also aimed at investigating the relation between overlearning-associated change in behavioral performance and brain activity. Thirteen schizophrenic patients and 13 healthy volunteers were studied with functional magnetic resonance imaging (fMRI) while performing a recently developed overlearning paradigm [Koch K, Wagner G, von Consbruch K, Nenadic I, Schultz C, Ehle C, Reichenbach J, Sauer H, Schlösser R (2006) Temporal changes in neural activation during practice of information retrieval from short-term memory: An fMRI study. Brain Res 1107:140-150]. Consistent with the earlier study, short-term learning of stimulus material was associated with significant performance improvements and exponential signal decreases in a fronto-parieto-cerebellar network both in schizophrenic patients and in healthy volunteers. Against expectation patients exhibited stronger signal decreases relative to controls in anterior cingulate (Brodmann area (BA) 32), middle and superior temporal (BA 37, BA 22), superior frontal (BA 8/9, BA 6) and posterior parietal regions (BA 40). Furthermore, the individually modeled exponential decay rate of the blood oxygenation level-dependent signal in the right dorsolateral prefrontal cortex was significantly correlated with exponential decrease in mean behavioral response times in healthy controls while a statistical trend emerged in patients. A relative hyperactivation in the patient group was observable only at the start of the learning process and diminished with continued overlearning. This effect might indicate a gradual reduction of recruited neuronal resources and a practice-associated activation normalization in patients with schizophrenia. Our data suggest that in subacute patients learning and associated decreases in cerebral activation brought about by short-term practice are left unimpaired.

A Jones matrix formalism for simulating three-dimensional polarized light imaging of brain tissue.

The neuroimaging technique three-dimensional polarized light imaging (3D-PLI) provides a high-resolution reconstruction of nerve fibres in human post-mortem brains. The orientations of the fibres are derived from birefringence measurements of histological brain sections assuming that the nerve fibres­consisting of an axon and a surrounding myelin sheath­are uniaxial birefringent and that the measured optic axis is oriented in the direction of the nerve fibres (macroscopic model). Although experimental studies support this assumption, the molecular structure of the myelin sheath suggests that the birefringence of a nerve fibre can be described more precisely by multiple optic axes oriented radially around the fibre axis (microscopic model). In this paper, we compare the use of the macroscopic and the microscopic model for simulating 3D-PLI by means of the Jones matrix formalism. The simulations show that the macroscopic model ensures a reliable estimation of the fibre orientations as long as the polarimeter does not resolve structures smaller than the diameter of single fibres. In the case of fibre bundles, polarimeters with even higher resolutions can be used without losing reliability. When taking the myelin density into account, the derived fibre orientations are considerably improved.

Quantitative estimation of 3-D fiber course in gross histological sections of the human brain using polarized light.

Series of polarized light images can be used to achieve quantitative estimates of the angles of inclination (z-direction) and direction (in xy-plane) of central nervous fibers in histological sections of the human brain. (1) The corpus callosum of a formalin-fixed human brain was sectioned at different angles of inclination of nerve fibers and at different thicknesses of the samples. The minimum, and maximum intensities, and their differences revealed a linear relationship to the angle of inclination of fibers. It was demonstrated that sections with a thickness of 80--120 microm are best suited for estimating the angle of inclination. (2) Afterwards the optic tracts of eight formalin-fixed human brains were sliced at different angles of fiber inclination at 100 microm. Measurements of intensity in 30 pixels in each section were used to calculate a linear function of calibration. The maximum intensities and the differences between maximum and minimum values measured with two polars only were best suited for estimation of fiber inclination. (3) Gross histological brain slices of formalin-fixed human brains were digitized under azimuths from 0 to 80 degrees using two polars only. These sequences were used to estimate the inclination of fibers (in z-direction). The same slices were digitized under azimuths from 0 to 160 degrees in steps of 20 degrees using a quarter wave plate additionally. These sequences were used to estimate the direction of the fibers in xy-direction. The method can be used to produce maps of fiber orientation in gross histological sections of the human brain similar to the fiber orientation maps derived by diffusion weighted magnetic resonance imaging.