1/227. A presenilin-1 Thr116Asn substitution in a family with early-onset Alzheimer's disease.mutation in the presenilin-1 (PS-1) gene at chromosome 14q24.3 is the most common cause of autosomal dominant early-onset Alzheimer's disease. Here, we report a novel missense mutation in the presenilin-1 gene found in a three-generation Danish family with autopsy-verified early-onset Alzheimer's disease. Two affected first-degree relatives in two generations were found to be heterozygous for a cytosine to adenine transversion at the second position of codon 116, which changes the amino acid at that position from threonine to asparagine. This conservative amino acid substitution occurs in an evolutionary highly conserved region of the PS-1 protein and is associated with onset of the disease between age 35 and 41 years and 4-8 years' duration of the disease. Analysis of amyloid beta-protein (A beta) deposition in brain specimens from one affected family member showed predominance of A beta 42(43). Onset and progression of the disease were very similar in two sibs homozygous for the epsilon 3 allele and the epsilon 4 allele, respectively, of the polymorphic apolipoprotein E locus. The lack of effect of the high risk epsilon 4/epsilon 4 genotype on the disease in this family corroborates and extends previous observations that the presence of one copy of the epsilon 4 allele does not modulate PS-1 associated Alzheimer's disease.- - - - - - - - - - ranking = 1keywords = amyloid (Clic here for more details about this article) |
2/227. A familial case of Alzheimer's disease without tau pathology may be linked with chromosome 3 markers.Alzheimer's disease is the most common form of dementia that occurs in later years. The diagnosis is confirmed by the pathological findings of betaA4-amyloid-containing neuritic plaques and neurofibrillary tangles, the former being present in sufficient quantity commensurate with age. Other forms of dementia are more difficult to diagnose clinically; their pathology is noted for the lack of plaques and tangles. A patient with a family history of dementia presented with the clinical signs of Alzheimer's disease which lasted for 13 years. At autopsy the brain tissue had betaA4-amyloid-containing neuritic plaques, but no neurofibrillary tangles (i.e., the tissue was negative for staining with the tau antibody). Genetic analysis of dna from family members revealed no linkage with chromosome 17 markers, indicating that this was not frontotemporal dementia. However, there was linkage with chromosome 3 markers. Thus, this form of Alzheimer's disease with a pathology of plaques only is linked with markers on chromosome 3.- - - - - - - - - - ranking = 2keywords = amyloid (Clic here for more details about this article) |
3/227. Mapping biochemistry to metabolism: FDG-PET and amyloid burden in Alzheimer's disease.We evaluated the relationship between amyloid-beta protein (A beta) concentration and the metabolic abnormality in an Alzheimer's disease (AD) patient as measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Across most regions there were significant inverse correlations among FDG-PET intensity values and both insoluble. The temporal lobe samples showed no significant correlation between FDG-PET values and A beta deposition. Findings support A beta as contributing to the hypometabolism in regions of the AD brain that are still relatively viable metabolically; those regions with chronic pathologic damage, such as temporal cortex, may have other factors that contribute to metabolic deficits.- - - - - - - - - - ranking = 5keywords = amyloid (Clic here for more details about this article) |
4/227. A follow-up study of the family with the Swedish APP 670/671 Alzheimer's disease mutation.OBJECTIVE: To study the progression of Alzheimer's disease (AD) at a very early stage and to evaluate clinical markers of presymptomatic AD. SETTING: Longitudinal study at a university hospital. SUBJECTS: A Swedish family harboring a double mutation at codons 670/671 of the APP gene on chromosome 21 was followed longitudinally for 3 years. Both mutation carriers and noncarriers participated. OUTCOME MEASUREMENTS: Results from clinical investigations, electroencephalography, neuropsychological and neuroradiological examinations including magnetic resonance imaging, single-photon emission computed tomography and positron emission tomography were assessed and compared on two or more occasions. MAIN OUTCOME: During follow-up, 1 initially asymptomatic mutation carrier who was near the expected age of onset for this family, developed cognitive symptoms, and at the end of the follow-up fulfilled the diagnostic criteria for AD. One mutation carrier with cognitive symptoms at the first examination showed clinical deterioration and was diagnosed with AD. One demented mutation carrier died and was shown to have typical AD neuropathology at autopsy. The two remaining asymptomatic mutation carriers, as well as all the noncarriers were asymptomatic. These mutation carriers who were near the expected age of onset of AD but without clinical signs of the disease, did not show changes in either electrophysiological parameters or volumes of the temporal lobes. However, in these 2 individuals the blood flow in the temporal lobe showed intermediate values between the symptomatic mutation carriers and healthy noncarriers. Two neuropsychological tests showed a deterioration that paralleled clinical symptoms in 1 of the mutation carriers who was close to the expected age of onset and who at the end of the follow-up had clinical signs of AD. In the same subject, brain glucose metabolism was pathologically reduced in the temporal lobes before other clinical symptoms were obvious. CONCLUSION: In this familial form of AD a reduced temporal lobe glucose metabolism was indicative of AD before the expected clinical onset. Reduced glucose metabolism even preceded the development of subjective or objective cognitive dysfunction and might therefore serve as a clinical marker for AD before the onset of clinical symptoms. Reduced cerebral blood flow in the temporal lobes and cognitive deterioration paralleled the clinical decline in the early stage of the disease. Copyrightz1999S.KargerAG,Basel- - - - - - - - - - ranking = 0.042606446552807keywords = cerebral (Clic here for more details about this article) |
5/227. Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy.OBJECTIVE: To clarify the phenotypic heterogeneity in deposition of amyloid beta (Abeta) in the parenchyma and in cerebral vessels of the brains of the patients having presenilin-1 (PS1) mutations. Mutations in PS1 induce increased production of Abeta42(43), resulting in an enhanced overall deposition of Abeta protein within the cerebral cortex. methods: sequence analysis of the PS1 gene of dna from patients with early onset Alzheimer's disease, and immunostaining of brain tissues by end specific monoclonal antibodies against Abeta. RESULTS: sequence analysis disclosed a novel mutation (N405S) in the PS1 gene in a Japanese patient with early-onset Alzheimer's disease. Postmortem examination of one patient with N405S showed limited cerebral amyloid angiopathy, whereas postmortem examination of another Japanese patient with Alzheimer's disease with the E184D mutation disclosed severe cerebral amyloid angiopathy. The brains of both patients showed widespread neuritic plaques, neurofibrillary tangles, and neuronal loss. Immunostaining showed that Abeta42 was predominant over Abeta40 in neuritic plaques in both patients, whereas Abeta40 was found to be predominant over Abeta42 in cerebral amyloid angiopathy in the patient with E184D. However, most cortical vessels of the patient with N405S were not reactive with either of the antibodies. CONCLUSION: The N405S mutation of PS1 is a major determinant of cortical Abeta deposition but not cerebral amyloid angiopathy in Alzheimer's disease.- - - - - - - - - - ranking = 1730.9773678966keywords = amyloid angiopathy, cerebral amyloid angiopathy, cerebral amyloid, angiopathy, amyloid, cerebral (Clic here for more details about this article) |
6/227. Anterior choroidal artery infarction presenting as a progressive cognitive deficit.PURPOSE: The authors describe a patient in whom neuroimaging using Tc-99m HMPAO SPECT, F-18 fluorodeoxyglucose (F-18 FDG) coincidence imaging, and magnetic resonance imaging (MRI) identified an anterior choroidal artery infarction. neuroimaging played a critical role in confirming this diagnosis, because the patient had symptoms of progressive cognitive decline and satisfied the National Institute of Neurological and Communicative Disorders and stroke-Alzheimer's disease and Related Disorders association criteria for Alzheimer's disease (AD). methods: Tc-99m HMPAO brain SPECT was performed using a triple-head gamma camera. F-18 FDG scanning was obtained 40 minutes after intravenous injection of 5 mCi F-18 FDG using a coincidence camera. A brain MRI scan was performed using a 1.5-Tesla scanner. RESULTS: Tc-99m HMPAO SPECT showed focal hypoperfusion to the right parahippocampal cortex. F-18 FDG coincidence imaging showed a more extensive reduction in glucose metabolism compared with SPECT. The MRI scan confirmed the presence of a small segmental choroidal artery infarction. The Tc-99m HMPAO and F-18 FDG scans were not consistent with AD. CONCLUSIONS: This case illustrates the value of the regional cerebral blood flow SPECT for evaluating memory impairment in the elderly. Decreased regional cerebral blood flow to the posterior temporoparietal region is consistent with AD, whereas regional cerebral blood flow diminution in a vascular territory is consistent with vascular dementia. In this case, the patient was clinically diagnosed with AD, and SPECT was performed to establish the baseline regional cerebral blood flow before the cholinesterase inhibitor donepezil was administered. An infarction was diagnosed on the regional cerebral blood flow brain SPECT scan, which was later confirmed by MRI. Infarctions of the parahippocampal cortex may resuft in memory impairment, which can appear clinically similar to AD.- - - - - - - - - - ranking = 0.21303223276404keywords = cerebral (Clic here for more details about this article) |
7/227. microglia and neuritic plaques in familial Alzheimer's disease induced by a new mutation of presenilin-1 gene. An ultrastructural study.The results of the ultrastructural study of the brains of two sisters with familial Alzheimer's disease (AD) induced by a new mutation of presenilin-1 (PS-1) gene who died at the young age (35 and 37 years) are presented. In both cases, the changes typical of AD with particularly large number of neuritic plaques (NPs) were found. Microglial cells were located between amyloid core and neurites. At the ultrastructural level, the content of microglial cytoplasm was differentiated (amyloid fibrils or/and phagocytic bodies). This may suggest that microglial cells participate in forming of amyloid fibrils and/or phagocytosis of amyloid.- - - - - - - - - - ranking = 4keywords = amyloid (Clic here for more details about this article) |
8/227. Cerebrovascular pathology in Alzheimer's disease and leukoaraiosis.A high percentage of patients with Alzheimer's disease (AD) show evidence of white matter degeneration known as leukoaraiosis (LA), which is due to chronic ischemia. We found that the periventricular veins tend to become occluded by multiple layers of collagen in the vessel walls in the elderly. This collagen deposition is particularly excessive in LA lesions. Therefore, it is present in the brains of many AD patients, along with other ischemia-causing cerebrovascular pathology. We found evidence that there is severe loss of oligodendrocytes in LA, due to extensive apoptosis. No evidence of inflammation was found in the LA lesions. In thick celloidin sections of AD brain, we have obtained detailed 3D views of small (early) deposits of amyloid (stained with beta-amyloid antibody) around capillaries (stained with collagen IV antibody).- - - - - - - - - - ranking = 2keywords = amyloid (Clic here for more details about this article) |
9/227. Vascular and metabolic reserve in Alzheimer's disease.Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.- - - - - - - - - - ranking = 0.085212893105614keywords = cerebral (Clic here for more details about this article) |
10/227. Glial intranuclear inclusion bodies in a patient with Alzheimer's disease.We report a case of dementia in an elderly woman with the pathological findings of Alzheimer's disease and numerous intranuclear inclusions in astrocytes and occasionally in neurons. These inclusions were seen in the cerebral cortex, limbic areas, basal ganglia, thalamus, brain stem and cerebellum. They expressed ubiquitin and were ultrastructurally composed of haphazardly arranged straight filaments. The presence of similar intranuclear inclusions in previous cases of adult-onset dementia without other neuropathological changes suggests an important link between these kind of inclusions and dementia. To our knowledge, this type of intranuclear inclusions has not been previously described in association with Alzheimer pathology.- - - - - - - - - - ranking = 0.042606446552807keywords = cerebral (Clic here for more details about this article) |
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