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- Haglund, Mattias, et al.
(författare)
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Cerebral amyloid angiopathy and cortical microinfarcts as putative substrates of vascular dementia.
- 2006
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 21:7, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Vascular dementia (VaD) has occasionally been associated with cerebral amyloid angiopathy (CAA), but the prevalence and significance of this counterintuitive relationship are poorly known. Therefore, we investigated the presence and characteristics of CAA in brains of VaD cases. Methods We examined temporal and parietal regions of the cerebral cortex of 26 consecutive VaD cases from the Lund Longitudinal Dementia Study. We carried out immunohistochemistry and routine stainings, determined Apolipoprotein E (ApoE) genotypes, and obtained clinical characteristics on the studied group for retrospective analysis. Results CAA was marked in eight out of 26 cases, and correlated strongly with the presence of cortical microinfarcts, both in the temporal lobe and in the parietal lobe. Based on comparisons with eight age-matched VaD cases without CAA, the clinical records suggested that VaD cases with CAA as a group exhibited less pronounced neurological symptoms. A clear contribution of the ApoE genotype could not be identified. Conclusions Based on a combination of the clinical and pathological data, we suggest that microinfarcts in the cerebral cortex associated with severe CAA may be the primary pathological substrate in a significant proportion of VaD cases. Future studies should be undertaken to confirm or dismiss the hypothesis that these cases exhibit a different symptom profile than VaD cases without CAA. Copyright (c) 2006 John Wiley & Sons, Ltd.
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| 2. |
- Haglund, Mattias, et al.
(författare)
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Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer's disease and vascular dementia.
- 2006
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 111:5, s. 430-435
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid angiopathy (CAA) caused by deposition of amyloid beta (A beta) peptides in the cerebrovasculature, involves degeneration of normal vascular components and increases the risk of infarction and cerebral hemorrhage. Accumulating evidence suggests that sporadic CAA is also a significant contributor to cognitive decline and dementia in the elderly. However, the mechanisms by which CAA arises are poorly understood. While neuronal sources of A beta peptides are sufficient to cause CAA in transgenic mice overexpressing the amyloid precursor protein, there is reason to believe that in aging man, vascular disease modulates the disease process. To better understand CAA mechanisms in dementia, we assessed the frontal cortex of 62 consecutive cases of Alzheimer's disease (AD), vascular dementia (VaD), and mixed dementia (MD) using immunohistochemistry with antibodies to A beta, smooth muscle actin and the carboxyl-terminal peptides to detect A beta(40) and A beta(42). While vascular A beta deposition was invariably associated with smooth muscle degeneration as indicated by absence of smooth muscle cell actin reactivity, VaD/MD cases exhibited markedly more vascular A beta(42) deposits and smooth muscle actin loss compared to AD cases with similar degrees of CAA and A beta(40) deposition. This suggests that distinct mechanisms are responsible for the differential deposition of A beta in CAA associated with AD and that associated with ischemic/cerebrovascular disease. It is plausible that experimental studies on the effects of cerebrovascular disease on A beta production and elimination will yield important clues on the pathogenesis of CAA.
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| 3. |
- Haglund, Mattias, et al.
(författare)
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Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible implications for diagnosis and treatment.
- 2006
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Ingår i: Neuropathology. - : Wiley. - 0919-6544 .- 1440-1789. ; 26:6, s. 528-532
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Tidskriftsartikel (refereegranskat)abstract
- Degeneration of the locus ceruleus (LC) and decreased cortical levels of norepinephrine are common findings in Alzheimer's disease (AD), but their significance is unknown. Because the noradrenergic system is accessible to pharmacological intervention, the role of LC degeneration and noradrenergic dysfunction in the pathogenesis and clinical manifestations of AD needs clarification. Hypothetically, loss of noradrenergic innervation could cause microvascular dysfunction and manifest as ischemia. The objectives of this study were to develop a scale for assessment of LC degeneration and to determine whether degeneration of the LC correlates quantitatively with either duration of clinical dementia, overall severity of AD pathology or with measures of ischemic non-focal white matter disease (WMD) in AD. This report is a pathological follow-up of a clinical longitudinal dementia study of 66 consecutive cases of AD without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were included for comparative purposes. No correlation between degree of LC degeneration and duration of dementia, AD or WMD severity was found. LC degeneration was significantly more severe in the AD group than in the VaD group. Even though LC degeneration was not associated with WMD or the severity of AD pathology in this AD material, we suggest that clinical studies on the consequences of noradrenergic dysfunction are warranted. Treatment augmenting noradrenergic signaling is available and safe. The marked difference in the level of LC degeneration between AD and VaD cases suggests that LC degeneration could be used as a diagnostic marker of AD.
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| 4. |
- Haglund, Mattias
(författare)
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Observations on cerebral amyloid angiopathy and microvascular pathology in Alzheimer's disease and vascular dementia
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dementia is a state of permanent loss of cognitive function, most commonly affecting the elderly. With a rapidly growing aged population, the spectrum of disorders that lead to dementia is exerting an ever-increasing toll on patients, families and society alike. The most common dementing disorders are Alzheimer's disease and vascular dementia. Although Alzheimer's disease is very common and was described almost a century ago, the pathomechanisms are imperfectly understood, and mainly symptomatic therapy is available. Treatment options are even more meagre in vascular dementia, but in many cases, this disorder can possibly be prevented by risk factor management. Since both Alzheimer's disease and vascular dementia are common in the elderly population, it is not uncommon for both diseases to be present to some degree in the same patient. Increasing evidence suggests that the disease mechanisms not only coexist, but that they interact synergistically, further exacerbating the clinical disorder. The purpose of this thesis was to explore features of vascular pathology in Alzheimer's disease and vascular dementia, to improve basic understanding of the disease processes in play. We have shown that one of the major hallmarks of Alzheimer's disease, deposition of amyloid protein in the cerebrovasculature (cerebral amyloid angiopathy), is surprisingly common in vascular dementia, and frequently more severe than in Alzheimer's disease. In Alzheimer's disease, cerebral amyloid angiopathy is associated with ischemic white matter disease, but in vascular dementia, cerebral amyloid angiopathy is associated with cortical microinfarctions. Furthermore, the interrelationship between the amyloid beta (A-beta) peptide species deposited is affected by the presence of cerebrovascular disease, which is associated with a relative increase in deposition of the more fibrillogenic and toxic variant of the Ab peptide, and more severe degeneration of vascular components.
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| 5. |
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| 6. |
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| 7. |
- Sjöbeck, Martin, et al.
(författare)
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White matter mapping in Alzheimer's disease: A neuropathological study.
- 2006
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 27:5, s. 673-680
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Tidskriftsartikel (refereegranskat)abstract
- White matter disease (WMD) with pervasive non-focal subtotal tissue loss is frequently seen in Alzheimer's disease (AD) upon neuropatholooical examination. Although WMD has varying effects on AD symptoms, accurate clinical detection is difficult due partly to scarcity of correlative structural imaging and histopathological studies. Neuropathological Studies of WMD severity and distribution have been conducted earlier using semi-quantitative methods. A technique for quantifying WMD objectively in large white matter areas, based on optical density (OD) measurements oil images of scanned whole-brain sections, was developed and was validated using conventional microscopic assessment. Altogether, 16 AD cases with concomitant WMD (AD-WMD) and 9 cases of AD without WMD (AD-only) were analysed. The OD values correlated significantly with the neuropathological severity of WMD and were significantly lower in AD-WMD than ill AD-only in frontal, frontoparietal, temporal and parietal white matter but not ill the occipital white matter, the frontal OD difference being greatest. Useful baseline information oil WMD distribution in AD to relate to in vivo imaging results was obtained. (c) 2005 Published by Elsevier Inc.
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