| 241. |
- Simonsen, A H, et al.
(författare)
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Amyloid beta1-40 quantification in CSF: comparison between chromatographic and immunochemical methods.
- 2007
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:4, s. 246-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Amyloid beta (Abeta) is the principal component of senile plaques, one of the hallmarks of Alzheimer's disease (AD). Evidence is accumulating that soluble aggregates (oligomers) of Abeta are important in the pathogenesis of AD. METHODS: We compared three different methods for quantification of the 40 amino acid form of Abeta (Abeta40) in CSF, two based on antibodies [ELISA and surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF) with antibody-coated arrays] and one based on direct binding of proteins to a protein array [SELDI-TOF and immobilized metal affinity [copper] (IMAC30)]. RESULTS: CSF Abeta40 concentration was only found to be significantly elevated in AD (127% of control levels; p=0.0095) using SELDI-TOF with IMAC30 arrays. CONCLUSIONS: These data suggest that the measured Abeta level in CSF may differ depending on whether antibody-based methods are used or not, possibly caused by epitope masking due to Abeta oligomerization or to binding of Abeta to carrier proteins.
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| 242. |
- Sjogren, M., et al.
(författare)
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Decreased CSF-ß-amyloid 42 in Alzheimer's disease and amyotrophic lateral sclerosis may reflect mismetabolism of ß-amyloid induced by disparate mechanisms
- 2002
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 13:2, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- Both tau and ß-amyloid 42 (Aß42) have been implicated in Alzheimer's disease (AD) and tau alone in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These proteins can be measured in the cerebrospinal fluid (CSF), differences from normal CSF levels may reflect pathophysiological mechanisms. Using ELISAs, we investigated the levels of total CSF-tau (here referred to as tau), phosphorylated CSF-tau (phospho-tau), and Aß42 in patients with AD (n = 19), FTD (n = 14), ALS (n = 11) and Parkinson's disease (PD, n = 15) and in age-matched controls (n = 17). Both CSF-tau and CSF-phosphotau were increased in AD compared with FTD (p < 0.001), ALS (p < 0.001), PD (p < 0.001) and controls (p < 0.001). CSF-Aß42 was markedly decreased in AD and ALS (both p < 0.001) and slightly decreased in FTD (p < 0.01) and PD (p < 0.05) compared with controls. Using CSF-phosphotau may improve the differentiation of AD from FTD and ALS in clinical praxis. Furthermore, decreased CSF-Aß42 levels may be common in neurode-generative disorders possibly reflecting changes in the metabolism of ß-amyloid or axonal degeneration. Copyright © 2002 S. Karger AG, Basel.
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| 243. |
- Sjogren, M, et al.
(författare)
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Negative neurofilament light and tau immunostaining in frontotemporal dementia
- 2004
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Ingår i: Frontotemporal Dementias 4th International Conference (Dementia and Geriatric Cognitive Disorders). - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 17:4, s. 346-349
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Konferensbidrag (refereegranskat)abstract
- We investigated the immunohistochemical stainability of phosphorylated tau and the light (NFL), intermediate (NFM), and heavy (NFH) neurofilament proteins in postmortem brain tissue from 8 patients with frontotemporal dementia (FTD), for comparison with 6 patients with Alzheimer's disease (AD), and 6 normal controls. In the FTD group, the neuropathological diagnosis was pure frontal-lobe degeneration of non-Alzheimer type (FLD) in 6 cases and in the remaining 2 cases mixed FLD-AD and frontal AD, respectively. The staining for tau was negative in 5 of the FLD cases and faintly positive in 1, but positive in all AD cases. The antibodies against NFM and NFH stained positive in FLD, AD, and controls, whereas the staining for NFL was negative in all FLD cases and positive in 1 AD case and in the controls. These findings regarding NFL and tau staining may be useful in the differential diagnosis of FLD and AD. Copyright (C) 2004 S. Karger AG, Basel.
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| 244. |
- Sjöbeck, Martin, et al.
(författare)
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Alzheimer's disease and the cerebellum: a morphologic study on neuronal and glial changes
- 2001
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:3, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- Structural manifestations of Alzheimer's disease (AD) including neuronal loss were investigated in 12 cases of AD and in 10 healthy age-matched controls, with focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the vermis and cerebellar hemispheres. Neurons were also counted in the inferior olivary nucleus. In vermis of the AD cases, the mean PC number was significantly lower (p = 0.019) than in the controls. The neurons in the inferior olive were similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and atrophy in the vermis was clearly severer in AD than in the controls. Features typical of cerebral Alzheimer encephalopathy (plaques, tangles and microvacuolization) were inconspicious. The structural cerebellar changes in the AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis. This may be reflected in some of the symptoms and signs seen in AD, signs that are generally overlooked or judged to be of noncerebellar origin.
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| 245. |
- Skoglund, Lena, et al.
(författare)
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No evidence of PGRN or MAPT gene dosage alterations in a collection of patients with frontotemporal lobar degeneration
- 2009
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 28:5, s. 471-475
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims Alterations in gene dosage have recently been associated with neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and deletions of the progranulin (PGRN) locus were recently described in patients with frontotemporal lobar degeneration (FTLD). FTLD is a genetically complex neurodegenerative disorder with mutations in the PGRN and the microtubule-associated protein tau (MAPT) genes being the most common known causes of familial FTLD. In this study, we investigated 39 patients with FTLD, previously found negative for mutations in PGRN and MAPT, for copy number alterations of these 2 genes. Methods Gene dosage analysis of PGRN and MAPT was performed using multiplex ligation-dependent probe amplification. Results We did not identify any PGRN or MAPT gene dosage variations in the 39 FTLD patients investigated. Conclusion We therefore conclude that alterations in gene copy number of PGRN and MAPT are not a cause of disease in this ollection of FTLD patients.
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| 246. |
- Skogseth, R, et al.
(författare)
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Neuropsychiatric correlates of cerebrospinal fluid biomarkers in Alzheimer's disease
- 2008
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 25:6, s. 559-563
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The aim of this study was to explore the relationship between cerebrospinal fluid biomarkers and neuropsychiatric symptoms in people with Alzheimer’s disease. Psychosis, agitation, apathy and depression were assessed using standardised measures in 32 patients with mild Alzheimer’s disease. <i>Methods:</i> The levels of the 42-amino-acid form of β-amyloid (Aβ<sub>1–42</sub>), tau and p-tau (phosphorylated at threonine 181) were quantified using the conventional enzyme-linked immunosorbent assay method. <i>Results:</i> Our result shows that apathy is significantly correlated with tau and p-tau but not with Aβ<sub>1–42</sub>. There were no significant correlations between indices of psychosis/agitation,or depression and cerebrospinal fluid Aβ<sub>1–42</sub>, tau or p-tau concentrations. <i>Conclusion:</i> Our finding suggests that apathy is associated with the level of neurofibrillary tangles in people with mild Alzheimer’s disease. In contrast, the overall levels of neurofibrillary tangles or amyloid plaques do not seem to be associated with depression or psychosis, indicating that other brain changes contribute to these symptoms.
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| 247. |
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| 248. |
- Small, BJ, et al.
(författare)
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Predictors of longitudinal changes in memory, visuospatial, and verbal functioning in very old demented adults
- 1998
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 9:5, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal changes in memory, visuospatial and verbal functioning in a sample of demented persons were examined. The role of several demographic, psychometric, and biological indices in predicting the rate of cognitive deterioration was also investigated. The sample consisted of 31 very old (mean age at entry = 83.5 years, range = 75–95) persons with Alzheimer’s disease (n = 22) and vascular dementia (n = 9) from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in verbal fluency and visuospatial ability, but only on 1 of 3 measures of episodic memory. Results from regression analyses indicated that a variety of putatively important variables, including age, gender, education, digit span, as well as a number of biological (vitamin B<sub>12</sub>, TSH), dementia etiology, and psychometric (digit span) indicators, exhibited no relationship to rate of memory, visuospatial, or verbal decline. The results suggest that the rate of cognitive deterioration in dementia is highly variable, and this variability in change appears to include a variety of characteristics. A possible reason thereof may be that the role of individual-difference variables for cognitive functioning in dementia is overshadowed by the pathogenetic process itself.
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| 249. |
- Solomon, A, et al.
(författare)
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Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:1, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- <i>Aims:</i> To investigate midlife cholesterol in relation to Alzheimer’s disease (AD) and vascular dementia (VaD) in a large multiethnic cohort of women and men. <i>Methods:</i> The Kaiser Permanente Northern California Medical Group (healthcare delivery organization) formed the database for this study. The 9,844 participants underwent detailed health evaluations during 1964–1973 at ages 40–45 years; they were still members of the health plan in 1994. AD and VaD were ascertained by medical records between 1 January 1994 and 1 June 2007. Cox proportional hazards models – adjusted for age, education, race/ethnic group, sex, midlife diabetes, hypertension, BMI and late-life stroke – were conducted. <i>Results:</i> In total, 469 participants had AD and 127 had VaD. With desirable cholesterol levels (<200 mg/dl) as a reference, hazard ratios (HR) and 95% CI for AD were 1.23 (0.97–1.55) and 1.57 (1.23–2.01) for borderline (200–239 mg/dl) and high cholesterol (≥240 mg/dl), respectively. HR and 95% CI for VaD were 1.50 (1.01–2.23) for borderline and 1.26 (0.82–1.96) for high cholesterol. Further analyses for AD (cholesterol quartiles, 1st quartile reference) indicated that cholesterol levels >220 mg/dl were a significant risk factor: HR were 1.31 (1.01–1.71; 3rd quartile, 221–248 mg/dl) and 1.58 (1.22–2.06; 4th quartile, 249–500 mg/dl). <i>Conclusion:</i> Midlife serum total cholesterol was associated with an increased risk of AD and VaD. Even moderately elevated cholesterol increased dementia risk. Dementia risk factors need to be addressed as early as midlife, before underlying disease(s) or symptoms appear.
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| 250. |
- Sonnesyn, H, et al.
(författare)
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High prevalence of orthostatic hypotension in mild dementia
- 2009
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 28:4, s. 307-313
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Orthostatic hypotension (OH) and QTc prolongation have potentially important prognostic and therapeutic consequences but have rarely been studied in patients with mild dementia. <i>Methods:</i> Patients with mild dementia were diagnosed according to consensus criteria after comprehensive standardized assessment. OH and QTc were assessed using standardized criteria. <i>Results:</i> OH was significantly more common in the dementia than in the control group, and systolic drop was higher in those with dementia with Lewy bodies. There were no significant differences in QTc values between dementia and control subjects. <i>Conclusion:</i> OH occurs even in patients with mild dementia, in particular in dementia with Lewy bodies. QTc was not prolonged in patients with mild dementia compared with normal controls.
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