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- Barrantes, Alejandro, et al.
(författare)
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Alzheimer’s Disease Amyloid Peptides Interact with DNA, As Proved by Surface Plasmon Resonance
- 2012
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Ingår i: Current Alzheimer Research. - : Bentham eBooks. - 1567-2050 .- 1875-5828. ; 9:8, s. 924-934
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Tidskriftsartikel (refereegranskat)abstract
- According to the amyloid hypothesis, abnormal processing of the β-amyloid precursor protein in Alzheimer's disease patients increases the production of β-amyloid toxic peptides, which, after forming highly aggregated fibrillar structures, lead to extracellular plaques formation, neuronal loss and dementia. However, a great deal of evidence has point to intracellular small oligomers of amyloid peptides, probably transient intermediates in the process of fibrillar structures formation, as the most toxic species. In order to study the amyloid-DNA interaction, we have selected here three different forms of the amyloid peptide: Aβ1-40, Aβ25-35 and a scrambled form of Aβ25-35. Surface Plasmon Resonance was used together with UV-visible spectroscopy, Electrophoresis and Electronic Microscopy to carry out this study. Our results prove that, similarly to the full length Aβ1-42, all conformations of toxic amyloid peptides, Aβ1-40 and Aβ25-35, may bind DNA. In contrast, the scrambled form of Aβ25-35, a non-aggregating and nontoxic form of this peptide, could not bind DNA. We conclude that although the amyloid-DNA interaction is closely related to the amyloid aggregation proneness, this cannot be the only factor which determines the interaction, since small oligomers of amyloid peptides may also bind DNA if their predominant negatively charged amino acid residues are previously neutralized.
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| 4. |
- Forsberg, A, et al.
(författare)
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High PIB Retention in Alzheimer's Disease is an Early Event with Complex Relationship with CSF Biomarkers and Functional Parameters
- 2010
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Ingår i: Current Alzheimer Research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 7:1, s. 56-66
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Tidskriftsartikel (refereegranskat)abstract
- Background:New in vivo amyloid PET imaging tracers, such as 11C-PIB, provide possibilities to deeper understand the underlying pathological processes in Alzheimers disease (AD). In this study we investigated how 11C-PIB retention is related to cerebral glucose metabolism, episodic memory and CSF biomarkers.Method:Thirty-seven patients with mild AD and 21 patients with mild cognitive impairment (MCI) underwent PET examinations with the amyloid tracer 11C-PIB, 18F-FDG for measurement of regional cerebral metabolic rate of glucose (rCMRglc), assessment of episodic memory and assay of cerebral spinal fluid (CSF) levels of amyloid-ß (Aβ1-42), total tau and phosphorylated tau respectively. Analyses were performed using Statistical Parametric Mapping (SPM) and regions of interest (ROIs).Results:Pooled data from AD and MCI patients showed strong correlations between 11C-PIB retention, levels of CSF biomarkers (especially Aß1-42), rCMRglc and episodic memory. Analysis of the MCI group alone revealed significant correlations between 11C-PIB retention and CSF biomarkers and between CSF biomarkers and episodic memory respectively. A strong correlation was observed in the AD group between rCMRglc and episodic memory as well as a significant correlation between 11C-PIB retention and rCMRglc in some cortical regions. Regional differences were observed as sign for changes in temporal patterns across brain regions.Conclusions:A complex pattern was observed between pathological and functional markers with respect to disease stage (MCI versus AD) and brain regions. Regional differences over time were evident during disease progression. 11C-PIB PET and CSF Aß1-42 allowed detection of prodromal stages of AD. Amyloid imaging is useful for early diagnosis and evaluation of new therapeutic interventions in AD.
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| 6. |
- Klein-Koerkamp, Yanica, et al.
(författare)
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Amygdalar atrophy in early Alzheimer's disease
- 2014
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Ingår i: Current Alzheimer Research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 11:3, s. 239-252
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Tidskriftsartikel (refereegranskat)abstract
- Current research suggests that amygdalar volumes in patients with Alzheimer's disease (AD) may be a relevant measure for its early diagnosis. However, findings are still inconclusive and controversial, partly because studies did not focus on the earliest stage of the disease. In this study, we measured amygdalar atrophy in 48 AD patients and 82 healthy controls (HC) by using a multi-atlas procedure, MAPER. Both hippocampal and amygdalar volumes, normalized by intracranial volume, were significantly reduced in AD compared with HC. The volume loss in the two structures was of similar magnitude (~24%). Amygdalar volume loss in AD predicted memory impairment after we controlled for age, gender, education, and, more important, hippocampal volume, indicating that memory decline correlates with amygdalar atrophy over and above hippocampal atrophy. Amygdalar volume may thus be as useful as hippocampal volume for the diagnosis of early AD. In addition, it could be an independent marker of cognitive decline. The role of the amygdala in AD should be reconsidered to guide further research and clinical practice. © 2014 Bentham Science Publishers.
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| 9. |
- Rizzuto, Debora, et al.
(författare)
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Dementia after age 75 : survival in different severity stages and years of life lost
- 2012
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Ingår i: Current Alzheimer Research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 9:7, s. 795-800
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Tidskriftsartikel (refereegranskat)abstract
- Dementia is a known predictor of mortality, but little is known about disease duration. We therefore aimed to investigate the impact of dementia on survival by estimating years lived with the disease, in total and in different severity stages, and by comparing dementia to other major chronic disorders such as cancer and cardiovascular disease (CVD). During a 7.4-year follow-up of the Kungsholmen project, 371 incident dementia cases of the 1,307 dementia-free persons, aged 75+ at baseline, were clinically diagnosed (DSM-III-R criteria). Diagnoses of cancer and CVD were obtained from the national Stockholm Inpatient Registry System, active since 1969. Disease duration, hazard ratio (HR), and potential years of life lost (PYLL) were derived from Kaplan-Meier survival estimation, the Cox model, and standard life-table analysis, respectively. Dementia was a significant predictor of mortality (HR=1.7; 95% CI: 1.47-1.92) after adjustment for several covariates including comorbidity, accounting for 16% of all deaths. The mean (�SD) survival time after dementia diagnosis was 4.1 (�2.6) years, and more than 2 years were spent in moderate (14-month) and severe (12-month) stages. Women with dementia lived longer than men, as they survived longer in the severe stage (2.1 vs. 0.5 years among 75-84-year-old women compared to coetaneous men). The PYLL were 3.4 for dementia, 3.6 for CVD, and 4.4 for cancer. We found a similar impact of dementia and CVD on survival, but following diagnosis, persons with dementia, and especially women, spent half of their remaining lives in the severe disabling stages of the disease.
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| 10. |
- Rolstad, Sindre, 1976, et al.
(författare)
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All cognitive systems but speed and visuospatial functions reduce the effect of CSF pathology on other systems.
- 2012
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Ingår i: Current Alzheimer research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 9:9, s. 1043-1049
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Tidskriftsartikel (refereegranskat)abstract
- The concept of reserve can be conceived as differences in the ability to compensate for pathology by recruiting additional or alternative networks. The purpose of this study was to examine whether certain cognitive systems may compensate for the effect of CSF amyloid beta 42 (Aβ42) and total tau (T-tau) on other cognitive systems. Five hundred and nine participants underwent neuropsychological examination and lumbar puncture. Multiple regression was performed with interaction terms to test whether a cognitive system reduced the impact of CSF pathology on other systems. All cognitive systems except speed and visuospatial functions were associated with reduced effects of T-tau and Aβ42 on semantic memory, working memory and visuospatial abilities. The burden of Aβ42 was reduced more often than that of T-tau. Our results suggest that most cognitive systems may be beneficial to maintenance of cognitive performance despite CSF burden. The results support the notion of cognitive reserve.
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