Amyloid (A ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer's disease to determine if intraneuronal A immunoreactivity is an early manifestation of Alzheimer-type pathology leading to Wbrillar plaque formation and/or neuroWbrillary degeneration. The appearance of A immunoreactivity in neurons in infants and stable neuron-type speciWc A immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4-13 aa and 8-17 aa of A in neurons indicated that intraneuronal A was mainly a product of -and -secretases (A 17-40/42 ). The presence of N-terminally truncated A 17-40 and A 17-42 in the control brains was conWrmed by Western blotting and the identity of A 17-40 was conWrmed by mass spectrometry. The prevalence of products of -and -secretases in neurons and -and -secretases in plaques argues against major contribution of A -immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal A 17-42 immunoreactivity was observed in structures with low susceptibility to Wbrillar A deposition, neuroWbrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimertype pathology. These observations indicate that the intraneuronal A immunoreactivity detected in this study is not a predictor of brain amyloidosis or neuroWbrillary degeneration. [389][390][391][392][393][394][395][396][397][398][399][400][401][402] 123 immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated A represents a product of normal neuronal metabolism.
The apoE phenotype of 83 patients with probable Alzheimer's disease (AD) and of 164 non-demented controls was determined by isoelectric focusing and Western blotting. The proportion of the epsilon 4 allele was 0.548 in AD and 0.202 in controls (P < 0.0001). The effect was seen in both early-onset and late-onset AD patients. The risk of AD in epsilon 4 homozygotes was 18-fold greater than in individuals without the epsilon 4 allele. ApoE concentrations were measured in serum and cerebrospinal fluid (CSF) from a subgroup of patients with AD (n = 72) and controls (n = 84) by a sandwich enzyme-linked immunosorbent assay. Although serum apoE concentrations were lower in individuals with the epsilon 4 allele than in those without the epsilon 4 allele, CSF apoE concentrations did not vary in different phenotype groups. However, CSF apoE levels were lower in AD patients than in controls. We conclude that the inheritance of the epsilon 4 allele of apoE is a risk factor for AD in the Finnish population.
This project involves the development of a fast semi-automatic segmentation procedure to make an accurate volumetric estimation of brain lesions. This method has been applied in the segmentation of demyelination plaques in Multiple Sclerosis (MS) and right cerebral hemispheric infarctions in patients with neglect. The developed segmentation method includes several image processing techniques, such as image enhancement, amplitude segmentation, and region growing. The entire program operates on a PC-based computer and applies graphical user interfaces. Twenty three patients with MS and 43 patients with right cerebral hemisphere infarctions were studied on a 0.5 T MRI unit. The MS plaques and cerebral infarctions were thereafter segmented. The volumetric accuracy of the program was demonstrated by segmenting Magnetic Resonance (MR) images of fluid filled syringes. The relative error of the total volume measurement based on the MR images of syringes was 1.5%. Also the repeatability test was carried out as inter-and intra-observer study in which MS plaques of six randomly selected patients were segmented. These tests indicated 7% variability in the inter-observer study and 4% variability in the intra-observer study. Average time used to segment and calculate the total plaque volumes for one patient was 10 min. This simple segmentation method can be utilized in the quantitation of anatomical structures, such as air cells in the sinonasal and temporal bone area, as well as in different pathological conditions, such as brain tumours, intracerebral haematomas and bony destructions.
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