| 1. |
- Brunnström, Hans, et al.
(författare)
-
Correlations of CSF tau and amyloid levels with Alzheimer pathology in neuropathologically verified dementia with Lewy bodies.
- 2013
-
Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 1099-1166 .- 0885-6230. ; 28:7, s. 738-744
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The presence of concomitant Alzheimer pathology has been linked to earlier death in cases with dementia with Lewy bodies (DLB). Recently, elevated cerebrospinal fluid (CSF) tau protein levels have been reported to be associated with shorter survival in clinically diagnosed DLB. Correlations between CSF biomarkers and neuropathological findings in DLB are missing. The aim of this study was to investigate correlations between CSF biomarker levels and histopathological findings, with a focus on concomitant Alzheimer pathology, in neuropathologically verified DLB cases. METHODS: The extent of neurofibrillary pathology (Braak stage), neuritic plaques (CERAD stage), Alzheimer pathology (PPAD9 stage) and cerebral amyloid angiopathy was assessed in 16 cases with DLB in whom total tau (T-tau), hyperphosphorylated tau and amyloid beta 1-42 (Aβ42) protein levels in CSF had been analyzed in vivo. Demographic and clinical data were collected. RESULTS: Both Braak and PPAD9 stages were inversely correlated with Aβ42 levels, whereas CERAD stage showed no significant correlations. Cerebral amyloid angiopathy correlated positively with T-tau and T-tau/Aβ42 ratio, and inversely with Aβ42 levels, but the group showed a very heterogeneous extent of cerebral amyloid angiopathy. CONCLUSIONS: The burden of concomitant Alzheimer pathology correlates with CSF Aβ42 but not with T-tau levels in cases with neuropathologically defined DLB. Copyright © 2012 John Wiley & Sons, Ltd.
|
|
| 2. |
- Ahlenius, Henrik, et al.
(författare)
-
Adaptor Protein LNK Is a Negative Regulator of Brain Neural Stem Cell Proliferation after Stroke.
- 2012
-
Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:15, s. 5151-5164
-
Tidskriftsartikel (refereegranskat)abstract
- Ischemic stroke causes transient increase of neural stem and progenitor cell (NSPC) proliferation in the subventricular zone (SVZ), and migration of newly formed neuroblasts toward the damaged area where they mature to striatal neurons. The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The adaptor protein LNK suppresses hematopoietic stem cell self-renewal, but its presence and role in the brain are poorly understood. Here we demonstrate that LNK is expressed in NSPCs in the adult mouse and human SVZ. Lnk(-/-) mice exhibited increased NSPC proliferation after stroke, but not in intact brain or following status epilepticus. Deletion of Lnk caused increased NSPC proliferation while overexpression decreased mitotic activity of these cells in vitro. We found that Lnk expression after stroke increased in SVZ through the transcription factors STAT1/3. LNK attenuated insulin-like growth factor 1 signaling by inhibition of AKT phosphorylation, resulting in reduced NSPC proliferation. Our findings identify LNK as a stroke-specific, endogenous negative regulator of NSPC proliferation, and suggest that LNK signaling is a novel mechanism influencing plastic responses in postischemic brain.
|
|
| 3. |
- Alafuzoff, Irina, et al.
(författare)
-
The need to unify neuropathological assessments of vascular alterations in the ageing brain : Multicentre survey by the BrainNet Europe consortium
- 2012
-
Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 47:11, s. 825-833
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we summarise the results after carrying out a large survey regarding the assessment of vascular alterations, both vessel changes and vascular lesions in an inter-laboratory setting. In total, 32 neuropathologists from 22 centres, most being members of BrainNet Europe (BNE), participated by filling out a questionnaire with emphasis on assessment of common vascular alterations seen in the brains of aged subjects. A certain level of harmonisation has been reached among BNE members regarding sectioning of the brain, harvesting of brain tissue for histology and staining used when compared to the survey carried out in 2006 by Pantoni and colleagues. The most significant variability was seen regarding the assessment of severity and of clinical significance of vascular alterations. Two strategies have recently been recommended regarding the assessment of vascular alterations in aged and demented subjects. The National Institute on Aging - Alzheimer's Association (NIA-AA) recommends the assessment of hippocampal sclerosis, vascular brain injury and microvascular lesions in 12 regions. Although this strategy will be easy to follow, the recommendations do not inform how the load of observed alterations should be assessed and when the observed lesions are of significance. Deramecourt and his colleagues recommend an assessment and semiquantitative grading of various pathologies in 4 brain regions. This strategy yielded a total score of 0 to 20 as an estimate of pathology load. It is, however, not clear which score is considered to be of clinical significance. Furthermore, in several BNE trials the semiquantitative assessment has yielded poor agreement rates; an observation that might negatively influence the strategy proposed by Deramecourt and his colleagues. In line with NIA-AA, a dichotomised approach of easily recognisable lesions in a standardised set of brain regions harvested for neuropathological assessment and applying reproducible sampling and staining strategies is recommended by BNE. However, a simple strategy regarding assessment of load of alteration is urgently needed to yield reproducible, and at the same time, comparable results between centres.
|
|
| 4. |
|
|
| 5. |
- Brunnström, Hans, et al.
(författare)
-
Cerebrospinal fluid biomarker results in relation to neuropathological dementia diagnoses.
- 2010
-
Ingår i: Alzheimer's & dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 6:2, s. 104-109
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical dementia diagnoses are not always consistent with neuropathological findings. As correct diagnosis is important for treatment and care, new diagnostic possibilities for dementia are in demand. Cerebrospinal fluid biomarkers should ideally be able to identify ongoing processes in the brain, but need to be further compared with neuropathological findings for evaluation of their diagnostic validity. METHODS: This study included 43 patients with a clinical dementia disorder. All patients were neuropathologically examined at the University Hospital in Lund, Sweden, during the years 2001-2008, and all had a lumbar puncture carried out as part of the clinical investigation during the time of cognitive impairment. RESULTS: Of eight patients, five with Alzheimer's disease had elevated total tau protein (T-tau) and decreased amyloid beta 1-42 protein (Abeta42), while both values for the other three patients were normal. Slightly elevated T-tau and/or decreased Abeta42 were also seen in several patients with other dementia diagnoses such as Lewy body disease, frontotemporal lobar degeneration and vascular dementia. Furthermore, T-tau levels did not differ markedly between patients with morphologically tau-positive and tau-negative frontotemporal lobar degeneration. Also, seven of nine patients with Creutzfeldt-Jacob disease exhibited pronounced elevation in T-tau concentration. CONCLUSION: From this rather limited study, being the first of its kind in Sweden, we may conclude that there is no perfect concordance between cerebrospinal fluid biomarker levels and pathological findings, which should be taken into account in the clinical diagnostic setting.
|
|
| 6. |
- Brunnström, Hans, et al.
(författare)
-
Comparison of four neuropathological scales for Alzheimer's disease.
- 2011
-
Ingår i: Clinical Neuropathology. - 0722-5091. ; 30:2, s. 56-69
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: There are several neuropathological scales for staging of Alzheimer pathology. The system proposed by Braak and Braak is based on the topographic distribution of neurofibrillary tangles and neuropil threads, while that of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is based on the quantity of neocortical neuritic plaques. A combination of the Braak and CERAD staging scales was recommended by the National Institute on Aging and Reagan Institute (NIA-RI). The Poly-Pathology Alzheimer's Disease assessment, nine areas (PPAD9) is a staging system based on the extent of neuronal degeneration, microvacuolization, cytoarchitectural disorder and gliosis, in addition to neurofibrillary tangles and neuritic plaques, in nine cerebral regions. The aim of the present study was to critically compare these four neuropathological staging scales. Methods: We assessed the Alzheimer pathology, using the four scales, in 43 patients with various dementia disorders, with focus on concordance and differences between the staging systems. Results: Comparing the staging systems, the Spearman's rho value for PPAD9 vs. Braak was 0.65, for PPAD9 vs. CERAD 0.72, for PPAD9 vs. NIA-RI 0.67, and for Braak vs. CERAD 0.46. Conclusion: The correlation between the neuropathological staging systems was suboptimal, and we conclude that the choice of staging system affects the evaluation of Alzheimer pathology, and hence the final diagnosis.
|
|
| 7. |
- Brunnström, Hans, et al.
(författare)
-
Differential degeneration of the locus coeruleus in dementia subtypes.
- 2011
-
Ingår i: Clinical Neuropathology. - 0722-5091. ; 30:3, s. 104-110
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Neuronal loss in the locus coeruleus (LC) is common in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). The aims of the present study were to investigate LC degeneration in different dementia disorders including vascular dementia (VaD) and frontotemporal lobar degeneration (FTLD), to compare LC degeneration with severity of pathology in AD and DLB/PDD, to further evaluate the usefulness of a previously presented scoring system and to examine the predictive value of macroscopic assessment of the LC. Methods: A horizontal mid-level section of the pons was examined in 200 neuropathologically examined cases with clinical dementia. A previous macroscopic assessment of the LC was performed in 149 of the cases. Results: Cases with DLB/ PDD and AD presented with the highest microscopic LC degeneration scores, with significant differences compared to combined AD + VaD, in turn with a higher score than VaD, FTLD and other dementia disorders. Interrater agreement (weighted kappa;) for LC degeneration scoring was 0.83 - 0.91. DLB/ PDD, AD and AD + VaD were the diagnoses for 85% of the cases with macroscopic LC depigmentation. Conclusion: LC degeneration, which may be macroscopically noted, often indicates synuclein and/or Alzheimer pathology among demented. When clinical information is scarce or inconsistent, a macroscopic assessment of the LC may facilitate focusing of the subsequent neuropathological investigation. Also, the semiquantitative scoring system is a reliable tool for histological assessment of LC degeneration.
|
|
| 8. |
- Brunnström, Hans, et al.
(författare)
-
History of depression prior to Alzheimer's disease and vascular dementia verified post-mortem.
- 2013
-
Ingår i: Archives of Gerontology and Geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 56:1, s. 80-84
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to analyze the medical history, with regards to previous remote depression, in patients with neuropathologically verified Alzheimer's disease (AD), vascular dementia (VaD) and mixed AD/VaD. The 201 patients included (115 AD, 44 VaD and 42 mixed AD/VaD) had been referred to the Psychogeriatric/Psychiatric Department, Lund University Hospital, for psychogeriatric investigation and were followed-up with clinical records and detailed information on psychiatric history prior to the onset of dementia. Depression was considered to exist when the patient had consulted a psychiatrist or physician and had been diagnosed with a "depressive episode" or "depression" and when anti-depressants and/or other specific treatments had been prescribed. Twenty patients (10%) had suffered from depression earlier in life well before the onset of dementia. Eight of the 9 AD patients with a previous diagnosis of depression had suffered from only one depressive episode and all had responded well to treatment, with complete recovery. In the VaD group, 8 out of 9 patients suffered two or more depressive episodes and only two recovered completely. Events with a possible significant relationship to depression were seen in 8 of the 9 AD patients but in only 1 of the 9 VaD patients. Psychotic symptoms were more common in VaD than in the AD group. The treatment modality of depression was similar in the groups. In conclusion, a history of depression prior to dementia is more common and more therapy-resistant in VaD than in AD.
|
|
| 9. |
- Brunnström, Hans, et al.
(författare)
-
Response to letter to the editor.
- 2010
-
Ingår i: The American Journal of Geriatric Psychiatry. - 1545-7214. ; 18:1, s. 92-93
-
Tidskriftsartikel (refereegranskat)
|
|
| 10. |
- Brunnström, Hans, et al.
(författare)
-
Staging of Lewy-related pathology in dementia
- 2012
-
Ingår i: Clinical Neuropathology. - 0722-5091. ; 31:4, s. 216-223
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Lewy-related pathology is the characteristic feature of Parkinson's disease with and without dementia and dementia with Lewy bodies (DLB). There are two neuropathological staging systems for Lewy-related pathology commonly employed today: the staging system for Parkinson-related pathology by Braak et al., and the staging system by the Consortium on DLB. There are also several modified systems based on these two scales. Methods: We applied a total of eight different staging systems for Lewy-related pathology to 36 consecutive demented patients with various dementia disorders. Results: The staging systems varied considerably in number of unclassifiable cases (range 0 - 16 out of 36 cases), while the diagnostic agreement between the systems that were able to classify all or the very majority of cases varied only slightly (weighted kappa 0.86 - 0.92 and Spearman's sigma 0.80 - 1.0). Conclusion: The different staging systems for Lewy-related pathology that exist today vary in staging procedure and proportion of unclassifiable cases. The choice of system may affect the stage of Lewy-related pathology and ultimately final diagnosis.
|
|
