| 1. |
- Axelman, K, et al.
(author)
-
Apolipoprotein E and alpha1-antichymotrypsin genotypes and age of onset of familial Alzheimer's disease
- 1999
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:1, s. 1-5
-
Journal article (peer-reviewed)abstract
- Apolipoprotein E (APOE) and α<sub>1</sub>-antichymotrypsin (ACT) genotype and allele frequency distribution were investigated in 113 familial Alzheimer’s disease (AD) cases. A significantly higher σ4 frequency was observed in patients with an age of onset between 55–64 and 65–74 years compared to individuals with later or earlier onset. No difference in ACT <i>A</i> allele frequency was seen in any onset group, nor was any influence of ACT genotypes on the age of onset observed. However, the mean age of onset was lowered by the presence of the ACT/AA and ACT/TT genotypes among APOE σ3/3 bearers. Possible APOE effects on age of onset were evaluated in 78 affected sib pairs. An earlier age of onset was observed in siblings with an σ4 allele compared to siblings without an σ4 allele. This supports the notion that the σ4 allele promotes an earlier age of onset. However, in siblings with the same APOE genotype, a wide range of onset was seen, indicating that unknown genetic or environmental factors affect the expression of AD.
|
|
| 2. |
- Axelman, K, et al.
(author)
-
Life situation, coping and quality of life in people with high and low risk of developing Alzheimer's disease
- 2003
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 16:4, s. 220-228
-
Journal article (peer-reviewed)abstract
- The psychosocial consequences of being at different risk for inheriting Alzheimer’s disease (AD) were investigated in a high-risk group (n = 106) and a low-risk group (n = 37). Non-affected individuals from families with AD in two or more generations answered questions about their life situation, quality of life and coping. Their answers were compared with a population sample (n = 408). The high-risk group assessed the quality of their personal relationships and everyday life higher than did the population sample. They also used less emotive and supportive coping strategies compared with the population sample. Nearly 90% in the high-risk group felt anxiety concerning their own risk or the risk of their children and grandchildren of developing AD. About 50% of the respondents complained about a lack of information. The pieces of information they asked for were early signs of the disease, treatment, and practical information on how to handle everyday life with an affected relative.
|
|
| 3. |
- Basun, H, et al.
(author)
-
Plasma levels of Abeta42 and Abeta40 in Alzheimer patients during treatment with the acetylcholinesterase inhibitor tacrine
- 2002
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 14:3, s. 156-160
-
Journal article (peer-reviewed)abstract
- Deregulation of amyloid precursor protein (APP) processing with increased production of amyloid β-peptide (Aβ) is considered to be a key pathogenic event in Alzheimer’s disease (AD). It has been suggested that stimulation of the muscarinic M<sub>1</sub> receptor subtype affects APP processing and leads to a change in Aβ concentration. To test the hypothesis that treatment with a cholinesterase inhibitor could change the levels of Aβ in plasma, we measured Aβ42 and Aβ40 plasma levels in AD subjects before tacrine treatment and at weeks 2 and 6 of treatment. Treatment with tacrine had no statistically significant effect on plasma Aβ42 and Aβ40 either at 2 weeks or at 6 weeks of administration compared to baseline levels. Plasma Aβ42 and Aβ40 levels showed large subject-to-subject variation but small variation within the same patient over the 3-sample interval. After 2 weeks of treatment with tacrine, there was a strong negative correlation between tacrine concentration and levels of Aβ42 (r = –0.64; p = 0.01) and Aβ40 (r = –0.55; p = 0.04). However, after 6 weeks there was no correlation between plasma concentrations of tacrine and Aβ42 (r = 0.33; p = 0.34) or Aβ40 (r = –0.22; p = 0.54) levels in plasma. After 2 weeks of treatment with an acetylcholinesterase inhibitor, we found a correlation between higher drug concentrations and lower β-amyloid levels. This might indicate an effect on APP metabolism with an increased α-cleavage. But after 6 weeks of drug treatment, there was no obvious drug effect on β-amyloid concentrations. This finding may indicate that compensatory mechanisms have started at 6 weeks and that no long-term effect on key pathological features in AD is to be expected by an inhibition of acetylcholinesterase.
|
|
| 4. |
- Blomberg, M, et al.
(author)
-
Cerebrospinal fluid tau levels increase with age in healthy individuals
- 2001
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:2, s. 127-132
-
Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) tau is a promising biochemical ante-mortem marker for Alzheimer’s disease (AD). Levels are increased in AD compared to other dementias, neurological diseases and healthy controls. An age-related decrease in both soluble tau and tau bound to paired helical filaments has been shown in brains from non-demented subjects. To study tau levels in normal ageing, we investigated CSF in 29 healthy individuals aged 45–80 years. A statistically significant increase in CSF tau with increasing age was found which might be caused by neuronal loss during normal ageing and redistribution of soluble tau from the brain into CSF. We could not demonstrate any influence by the APOE genotype, though larger populations have to be investigated to confirm this result. In conclusion, we found an age-dependent increase in CSF tau in healthy individuals. We emphasise the importance of establishing an age-dependent interval of CSF tau in non-demented subjects.
|
|
| 5. |
- Bronge, L, et al.
(author)
-
White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype
- 1999
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:2, s. 89-96
-
Journal article (peer-reviewed)abstract
- To analyse the influence of apolipoprotein E (APOE) genotype on the extent of white matter lesions (WMLs) in Alzheimer’s disease (AD), we examined 60 AD patients with magnetic resonance imaging. The WMLs were rated visually in different brain regions. The patients with the APOE genotype σ4/4 had more extensive WMLs in the deep white matter than patients with genotypes σ3/3 and σ3/4. There was a correlation with age for WMLs in the deep white matter in patients with the APOE σ3/3 genotype. In patients carrying at least one σ4 allele, the WMLs showed no age correlation. The results could imply that in APOE allele σ4 carriers, the WMLs represent a pathological process related to the aetiology of the disease.
|
|
| 6. |
- Davidsson, P, et al.
(author)
-
Reduced expression of amyloid precursor protein, presenilin-1 and rab3a in cortical brain regions in Alzheimer's disease
- 2001
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:4, s. 243-250
-
Journal article (peer-reviewed)abstract
- To study the role of amyloid precursor protein (APP) in the pathogenesis of Alzheimer’s disease (AD), the level of APP was analysed by quantitative immunoblotting in 6 AD patients and 6 age-matched controls in 9 brain regions. These were associative cortices (orbital frontal cortex, inferior temporal cortex, inferior parietal cortex), primary cortex (occipital cortex), limbic structures (anterior cingulate gyrus, hippocampus), subcortical structures (putamen, thalamus) and cerebellum. To assess a potential relationship between APP and presenilin-1 (PS-1) and/or synaptic proteins, the levels of PS-1 and rab3a, a specific synaptic vesicle protein, were also determined in the same tissue samples. The level of APP was almost the same in the association cortical regions, primary cortex, and limbic structures and in the subcortical structures, while the lowest level was found in the cerebellum. There were more marked differences in the level of PS-1 and rab3a between different brain regions. The highest levels of PS-1 and rab3a were found in the association cortical areas, while intermediate levels were found in primary cortex, limbic structures and subcortical structures. As for APP, the lowest level was found in cerebellum. We found significantly reduced levels of all three proteins in the association cortices and in hippocampus in AD. Our data show that the protein levels are reduced in specific areas, restricted to neuronal populations that are known to degenerate in AD. Due to the similarity of the expression of APP, PS-1 and rab3a, it is tempting to speculate whether there is a functional relationship between these proteins.
|
|
| 7. |
- Ingelson, M, et al.
(author)
-
Tau immunoreactivity detected in human plasma, but no obvious increase in dementia
- 1999
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:6, s. 442-445
-
Journal article (peer-reviewed)abstract
- <i>Tau</i> proteins are central to the neuropathology of Alzheimer’s disease and <i>tau</i> levels in cerebrospinal fluid are elevated in affected individuals. In this study, we investigated the presence of <i>tau</i> in plasma from subjects with Alzheimer’s disease (n = 16), frontotemporal dementia (n = 10), vascular dementia (n = 16) and from healthy controls (n = 15). By using an ELISA with monoclonal <i>tau</i> antibodies, <i>tau</i> immunoreactivity was detected in approximately 20% of the subjects. However, no difference between the disease and control groups was seen. After gel filtration of <i>tau</i> immunopositive plasma, the peak reactivity was found in the 160-kD fraction, indicating the source to be <i>tau</i>-like molecules of high-molecular-weight or polymers of low-molecular-weight <i>tau</i> isoforms. We conclude that measurements of <i>tau</i> in plasma cannot be utilized diagnostically for Alzheimer’s disease or for the other dementias investigated.
|
|
| 8. |
- Kowalska, A, et al.
(author)
-
Lack of association between an intronic polymorphism in the presenilin-1 gene and sporadic late-onset Alzheimer disease in Polish patients
- 1998
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 9:3, s. 137-139
-
Journal article (peer-reviewed)abstract
- The apolipoprotein E (APOE) gene has in many studies been identified as a susceptibility factor in Alzheimer’s disease (AD). The APOE association is rather strong, but other not yet identified genetic factors are assumed to be involved in the pathogenesis of AD. Recently an association between an intronic polymorphism in presenilin-1 (PS-1) gene and late-onset AD was claimed. In order to confirm this observation we studied a sample of Polish patients with sporadic AD. However, our results did not confirm the existence of an association between the intronic polymorphism in the PS-1 gene and late-onset AD.
|
|
| 9. |
- Mustafa, A, et al.
(author)
-
Decreased plasma insulin-like growth factor-I level in familial Alzheimer's disease patients carrying the Swedish APP 670/671 mutation
- 1999
-
In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 10:6, s. 446-451
-
Journal article (peer-reviewed)abstract
- The plasma insulin-like growth factor I (IGF-I) level was determined in family members carrying the Swedish amyloid precursor protein (APP) 670/671 mutation with or without Alzheimer’s disease (AD) and in age-matched controls from the same family. Plasma growth hormone (GH) and prolactin (PRL) levels were also determined. Measurement of the plasma IGF-I level by radioimmunoassay revealed a significant reduction only in the family members with AD compared to age-matched controls. However, there was no significant difference in the levels of GH and PRL between the mutation carriers with or without AD and their respective age-matched controls. These findings indicate that the mechanism(s) regulating GH and PRL were preserved and those regulating IGF-I levels might be affected in AD patients with the Swedish APP 670/671 mutation.
|
|
| 10. |
|
|
