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Libard, S. & Alafuzoff, I. (2019). Alzheimer's disease neuropathological change and loss of matrix/neuropil in patients with idiopathic Normal Pressure Hydrocephalus, a model of Alzheimer's disease. Acta neuropathologica communications, 7, Article ID 98.
Open this publication in new window or tab >>Alzheimer's disease neuropathological change and loss of matrix/neuropil in patients with idiopathic Normal Pressure Hydrocephalus, a model of Alzheimer's disease
2019 (English)In: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 7, article id 98Article in journal (Refereed) Published
Abstract [en]

Here, we assessed unique brain tissue samples, obtained from living subjects with idiopathic Normal Pressure Hydrocephalus (iNPH). Our cohort of 95 subjects with age ranging from 75 to 79 years, displayed a high prevalence of beta-amyloid (A beta) and hyperphosphorylated t (HPt) pathology (63 and 61%, respectively) in a frontal cortex biopsy obtained during shunt operation. These lesions, i.e., Alzheimer's Disease Neuropathologic Change (ADNC), increased within 5 years and were more frequent in females. The extent of HPt pathology was sparse, primarily seen as neurites and stained dots. Noteworthy, concomitant pathology was seen in 49% of the whole cohort, indicating a severity of ADNC corresponding to a low/intermediate level following the current recommendations. This observation is predictable as based on previous publications a substantial number of subjects with iNPH over time develop AD. Thus, iNPH can be considered as a model of AD. We noted a surprisingly remarkable neuronal preservation assessing Neuronal Nuclei (NeuN) in parallel with a substantial depletion of matrix/neuropil. This finding is intriguing as it suggests that loss of matrix/neuropil might be one of the first lesion of ADNC but also a hallmark lesion of iNPH. The latter observation is in line with the enlarged ventricles, a cardinal feature of iNPH. Furthermore, a positive correlation was observed between the extent of A beta and NeuN but only in females indicating a neuronal preservation even when A beta pathology is present. The assessment of a surgical biopsy as described here is certainly informative and thus it is surprising that a neuropathologic assessment in the setting of iNPH, while inserting a shunt, is seldom performed. Here, we observed ADNC and surprisingly remarkable neuronal preservation in a substantial number of iNPH subjects. Thus, these subjects allow us to observe the natural course of the disease and give us an opportunity for intervention at the earliest stages of AD, prior to severe neuronal damage.

Place, publisher, year, edition, pages
BioMed Central, 2019
Keywords
Alzheimer's disease Neuropathologic change, Idiopathic Normal pressure hydrocephalus, Neuronal loss, Matrix/neuropil, Immunohistochemistry
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:uu:diva-390602 (URN)10.1186/s40478-019-0748-9 (DOI)000473753900001 ()31142354 (PubMedID)
Funder
Hans-Gabriel och Alice Trolle-Wachtmeisters stiftelse för medicinsk forskning
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-13Bibliographically approved
Rinne, J. O., Suotunen, T., Rummukainen, J., Herukka, S.-K., Nerg, O., Koivisto, A. M., . . . Leinonen, V. (2019). [C-11]PIB PET Is Associated with the Brain Biopsy Amyloid-beta Load in Subjects Examined for Normal Pressure Hydrocephalus. Journal of Alzheimer's Disease, 67(4), 1343-1351
Open this publication in new window or tab >>[C-11]PIB PET Is Associated with the Brain Biopsy Amyloid-beta Load in Subjects Examined for Normal Pressure Hydrocephalus
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 4, p. 1343-1351Article in journal (Refereed) Published
Abstract [en]

Background: Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-beta (A beta) pathology. Objective: To compare the [C-11]PIB PET uptake in the patients with suspected iNPH to A beta and hyperphosphorylated-tau (HP tau) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) A beta, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Methods: Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for A beta and HP tau in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [C-1(1)]PIB PET. A beta, total tau, and P tau(181) were measured by ELISA from the ventricular (n= 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3 +/- 2.4 years, range 3-1). Results: [C-11]PIB uptake in the right frontal cortex (rho = 0.60, p < 0.01) and the combined neocortical [C-11]PIB uptake score (rho = 0.61, p < 0.01) were associated with a higher A beta load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [C-11]PIB uptake was also associated with the ventricular CSF A beta (rho = -0.58, p = 0.03). Conclusions: The findings show that [C-11]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of A beta pathology in the patients with iNPH might also warrant treatment with current AD drugs.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Amyloid, brain biopsy, cerebrospinal fluid, normal pressure hydrocephalus, positron emission tomography
National Category
Neurology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-379776 (URN)10.3233/JAD-180645 (DOI)000460435000021 ()30689567 (PubMedID)
Available from: 2019-03-21 Created: 2019-03-21 Last updated: 2019-03-29Bibliographically approved
Friberg, N., Ljungberg, O., Berglund, E., Berglund, D., Ljungberg, R., Alafuzoff, I. & Englund, E. (2019). Cause of death and significant disease found at autopsy. Virchows Archiv, 475(6), 781-788
Open this publication in new window or tab >>Cause of death and significant disease found at autopsy
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2019 (English)In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 475, no 6, p. 781-788Article in journal (Refereed) Published
Abstract [en]

The use of clinical autopsy has been in decline for many years throughout healthcare systems of developed countries despite studies showing substantial discrepancies between autopsy results and pre-mortal clinical diagnoses. We conducted a study to evaluate over time the use and results of clinical autopsies in Sweden. We reviewed the autopsy reports and autopsy referrals of 2410 adult (age > 17) deceased patients referred to two University hospitals in Sweden during two plus two years, a decade apart. There was a decline in the number of autopsies performed over time, however, mainly in one of the two hospitals. The proportion of autopsy referrals from the emergency department increased from 9 to 16%, while the proportion of referrals from regular hospital wards was almost halved. The autopsies revealed a high prevalence of cardiovascular disease, with myocardial infarction and cerebrovascular lesion found in 40% and 19% of all cases, respectively. In a large proportion of cases (> 30%), significant findings of disease were not anticipated before autopsy, as judged from the referral document and additional data obtained in some but not all cases. In accordance with previous research, our study confirms a declining rate of autopsy even at tertiary, academic hospitals and points out factors possibly involved in the decline.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Autopsy, Cause of death, Diagnostic error, Referral quality
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-397789 (URN)10.1007/s00428-019-02672-z (DOI)000494381500001 ()31691009 (PubMedID)
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved
Libard, S., Cerjan, D. & Alafuzoff, I. (2019). Characteristics of the tissue section that influence the staining outcome in immunohistochemistry. Histochemistry and Cell Biology, 151(1), 91-96
Open this publication in new window or tab >>Characteristics of the tissue section that influence the staining outcome in immunohistochemistry
2019 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 151, no 1, p. 91-96Article in journal (Refereed) Published
Abstract [en]

Immunohistochemistry (IHC) is influenced by several factors such as cold ischemia time, fixative, fixation time, paraffin, storage time, antibody, antigen retrieval technique and detection systems. In the setting of post-mortem tissue, not only post-mortem delay, but also agonal state is of interest. Here, we assessed an additional variable, i.e., the thickness of the section, and noted that this variable also influenced the IHC outcome. This is of significance when the extent of labelling is a parameter to be assessed, for example when assigning a stage or grade of a disease. Furthermore, when assessing brain tissue with neurons, soma measuring from 4 to 100 µm, various cellular compartments composed of different proteins are localised in sections measuring 4 or 7 µm. Thus, what is seen in a 7-µm-thick section might be lacking in a 4-µm-thick section. Lack of information regarding the molecular size of commercial antibodies is also disturbing as this parameter might influence the distribution of the molecule in the three-dimensional section. The choice of antibody to be used and the staining methodology have been acknowledged being of significance for IHC outcome; however, neither sections thickness or the molecular weight has been discussed sufficiently. IHC has been shown to be an unpredictable technique used for assessment of tissue. This emphasises the need for detailed methodological descriptions in publications, the need to acknowledge and to harmonize all eventual pitfalls related to this methodology.

Keywords
Extent of staining, Immunohistochemistry, Pitfalls, Thickness of a section
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372540 (URN)10.1007/s00418-018-1742-1 (DOI)000455442800009 ()30357509 (PubMedID)
Funder
Hans-Gabriel och Alice Trolle-Wachtmeisters stiftelse för medicinsk forskning
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-03-29Bibliographically approved
Lundström, Y., Lundström, P., Popova, S., Lindblom, R. P. .. & Alafuzoff, I. (2019). Detection of Changes in Immunohistochemical Stains Caused by Postmortem Delay and Fixation Time. Applied immunohistochemistry & molecular morphology (Print), 27(3), 238-245
Open this publication in new window or tab >>Detection of Changes in Immunohistochemical Stains Caused by Postmortem Delay and Fixation Time
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2019 (English)In: Applied immunohistochemistry & molecular morphology (Print), ISSN 1541-2016, E-ISSN 1533-4058, Vol. 27, no 3, p. 238-245Article in journal (Refereed) Published
Abstract [en]

In this study, we have systematically assessed the influence of postmortem delay (PMD) and fixation time (FT) on the immunohistochemical (IHC) staining outcome. The IHC method is frequently applied on surgical and postmortem samples in diagnostics and research. To replicate the routine situation, brain tissues from pigs were exposed to either storage in a refrigerator (+8°C), that is, PMD (1 to 168 h), or fixed in 10% buffered formalin, that is, FT (18 to 94 d). Subsequently, the tissue was routinely processed into paraffin blocks to enable construction of tissue microarrays (TMA). Sections cut from the TMA blocks were stained applying 13 different antibodies directed against neuronal and glial antigens. Immunoreactivity applying 5 antibodies was influenced by prolonged PMD and applying 2 antibodies by prolonged FT. None of the staining outcomes related to the PMD or FT were predictable. Loss of TMA cores during processing was primarily influenced by pretreatment and by tissue characteristics (gray/white matter). The test model described here confirmed that these 2 variables, PMD and FT, indeed influence the IHC outcome. The PMD and FT are particularly of importance while assessing tissue samples obtained at autopsy. The result above is also of importance while comparing the IHC outcomes seen in the postmortem setting (various PMD/FT) with surgical samples or with IHC outcome seen in experimental animal setting (controlled PMD/FT). Thus, we suggest that the test model described here is considered when assessing the reliability of the IHC outcome when analyzing tissues with various characteristics.

Keywords
immunohistochemistry, tissue microarray, fixation time, postmortem delay
National Category
Other Basic Medicine Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-369701 (URN)10.1097/PAI.0000000000000658 (DOI)000462177700013 ()29912765 (PubMedID)
Funder
Hans-Gabriel och Alice Trolle-Wachtmeisters stiftelse för medicinsk forskning
Available from: 2018-12-16 Created: 2018-12-16 Last updated: 2019-04-24Bibliographically approved
Hellström, J., Romanos Zapata, R., Libard, S., Wikström, J., Ortiz-Nieto, F., Alafuzoff, I. & Raininko, R. (2019). Evaluation of the INTERPRET decision-support system: can it improve the diagnostic value of magnetic resonance spectroscopy of the brain?. Neuroradiology, 61(1), 43-53
Open this publication in new window or tab >>Evaluation of the INTERPRET decision-support system: can it improve the diagnostic value of magnetic resonance spectroscopy of the brain?
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2019 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 61, no 1, p. 43-53Article in journal (Refereed) Published
Abstract [en]

Purpose: We evaluated in a clinical setting the INTERPRET decision-support system (DSS), a software generated to aid in MRS analysis to achieve a specific diagnosis for brain lesions.

Methods: The material consisted of 100 examinations of focal intracranial lesions with confirmed diagnoses. MRS was obtained at 1.5 T using TE 20–30 ms. Data were processed with the LCModel for conventional analysis. The INTERPRET DSS 3.1. was used to obtain specific diagnoses. MRI and MRS were reviewed by one interpreter. DSS analysis was made by another interpreter, in 80 cases by two interpreters. The diagnoses were compared with the definitive diagnoses. For comparisons between DSS, conventional MRS analysis, and MRI, the diagnoses were categorised: high-grade tumour, low-grade tumour, non-neoplastic lesion.

Results: Interobserver agreement in choosing the diagnosis from the INTERPRET database was 75%. The diagnosis was correct in 38/100 cases, incorrect in 57 cases. No good match was found in 5/100 cases. The diagnostic category was correct with DSS/conventional MRS/MRI in 67/58/52 cases, indeterminate in 5/8/20 cases, incorrect in 28/34/28 cases. Results with DSS were not significantly better than with conventional MRS analysis. All definitive diagnoses did not exist in the INTERPRET database. In the 61 adult patients with the diagnosis included in the database, DSS/conventional MRS/MRI yielded a correct diagnosis category in 48/32/29 cases (DSS vs conventional MRS: p = 0.002, DSS vs MRI: p = 0.0004).

Conclusion: Use of the INTERPRET DSS did not improve MRS categorisation of the lesions in the unselected clinical cases. In adult patients with lesions existing in the INTERPRET database, DSS improved the results, which indicates the potential of this software with an extended database.

Keywords
Brain, Computer-aided diagnosis, Decision-support system, Magnetic resonance imaging, Magnetic resonance spectroscopy
National Category
Radiology, Nuclear Medicine and Medical Imaging Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-366791 (URN)10.1007/s00234-018-2129-7 (DOI)000456076500010 ()30443796 (PubMedID)
Available from: 2018-11-24 Created: 2018-11-24 Last updated: 2019-03-29Bibliographically approved
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R. ., Boyle, P. A., Arfanakis, K., . . . Schneider, J. A. (2019). Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report. Brain, 142, 1503-1527
Open this publication in new window or tab >>Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report
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2019 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 142, p. 1503-1527Article, review/survey (Refereed) Published
Abstract [en]

We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, similar to 25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy. Given that the oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.

Keywords
PET, MRI, FTLD, epidemiology, SNAP
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:uu:diva-393763 (URN)10.1093/brain/awz099 (DOI)000481419700013 ()31039256 (PubMedID)
Note

A correction has been published: Brain, Volume 142, Issue 7, July 2019, Page e37, https://doi.org/10.1093/brain/awz163

Available from: 2019-09-27 Created: 2019-09-27 Last updated: 2019-09-27Bibliographically approved
Luikku, A. J., Hall, A., Nerg, O., Koivisto, A. M., Hiltunen, M., Helisalmi, S., . . . Leinonen, V. (2019). Predicting Development of Alzheimer's Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus. Journal of Alzheimer's Disease, 71(4), 1233-1243
Open this publication in new window or tab >>Predicting Development of Alzheimer's Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 71, no 4, p. 1233-1243Article in journal (Refereed) Published
Abstract [en]

Background: Idiopathic normal pressure hydrocephalus (iNPH) patients often develop Alzheimer's disease (AD) related brain pathology. Disease State Index (DSI) is a method to combine data from various sources for differential diagnosis and progression of neurodegenerative disorders.

Objective: To apply DSI to predict clinical AD in shunted iNPH-patients in a defined population.

Methods: 335 shunted iNPH-patients (median 74 years) were followed until death (n = 185) or 6/2015 (n = 150). DSI model (including symptom profile, onset age of NPH symptoms, atrophy of medial temporal lobe in CT/MRI, cortical brain biopsy finding, and APOE genotype) was applied. Performance of DSI model was evaluated with receiver operating characteristic (ROC) curve analysis.

Results: A total of 70 (21%) patients developed clinical AD during median follow-up of 5.3 years. DSI-model predicted clinical AD with moderate effectiveness (AUC= 0.75). Significant factors were cortical biopsy (0.69), clinical symptoms (0.66), and medial temporal lobe atrophy (0.66).

Conclusion: We found increased occurrence of clinical AD in previously shunted iNPH patients as compared with general population. DSI supported the prediction of AD. Cortical biopsy during shunt insertion seems indicated for earlier diagnosis of comorbid AD.

Keywords
Alzheimer's disease, computer-assisted diagnosis, normal pressure hydrocephalus
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-398155 (URN)10.3233/JAD-190334 (DOI)000490569300016 ()31498122 (PubMedID)
Funder
Academy of Finland, 263193EU, FP7, Seventh Framework Programme, 601055EU, FP7, Seventh Framework Programme, 611005
Available from: 2019-12-05 Created: 2019-12-05 Last updated: 2019-12-10Bibliographically approved
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R. ., Boyle, P. A., Arfanakis, K., . . . Schneider, J. A. (2019). Reply: LATE to the PART-y [Letter to the editor]. Brain, 142, Article ID e48.
Open this publication in new window or tab >>Reply: LATE to the PART-y
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2019 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 142, article id e48Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-397211 (URN)10.1093/brain/awz226 (DOI)000493087300002 ()31359039 (PubMedID)
Available from: 2019-11-20 Created: 2019-11-20 Last updated: 2019-11-20Bibliographically approved
Abu Hamdeh, S., Virhammar, J., Sehlin, D., Alafuzoff, I., Cesarini, K. G. & Marklund, N. (2018). Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus. Journal of Neurosurgery, 1-9
Open this publication in new window or tab >>Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus
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2018 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, p. 1-9Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE The authors conducted a study to test if the cortical brain tissue levels of soluble amyloid beta (Aβ) reflect the propensity of cortical Aβ aggregate formation and may be an additional factor predicting surgical outcome following idiopathic normal pressure hydrocephalus (iNPH) treatment. METHODS Highly selective ELISAs (enzyme-linked immunosorbent assays) were used to quantify soluble Aβ40, Aβ42, and neurotoxic Aβ oligomers/protofibrils, associated with Aβ aggregation, in cortical biopsy samples obtained in patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt surgery. Patients underwent pre- and postoperative (3-month) clinical assessment with a modified iNPH scale. The preoperative CSF biomarkers and the levels of soluble and insoluble Aβ species in cortical biopsy samples were analyzed for their association with a favorable outcome following the VP shunt procedure, defined as a ≥ 5-point increase in the iNPH scale. RESULTS The brain tissue levels of Aβ42 were negatively correlated with CSF Aβ42 (Spearman's r = -0.53, p < 0.05). The Aβ40, Aβ42, and Aβ oligomer/protofibril levels in cortical biopsy samples were higher in patients with insoluble cortical Aβ aggregates (p < 0.05). The preoperative CSF Aβ42 levels were similar in patients responding (n = 11) and not responding (n = 9) to VP shunt treatment at 3 months postsurgery. In contrast, the presence of cortical Aβ aggregates and high brain tissue Aβ42 levels were associated with a poor outcome following VP shunt treatment (p < 0.05). CONCLUSIONS Brain tissue measurements of soluble Aβ species are feasible. Since high Aβ42 levels in cortical biopsy samples obtained in patients with iNPH indicated a poor surgical outcome, tissue levels of Aβ species may be associated with the clinical response to shunt treatment.

Keywords
AD = Alzheimer’s disease, Alzheimer’s disease, Aβ = amyloid beta, Aβ oligomers, ELISA = enzyme-linked immunosorbent assay, HPtau = hyperphosphorylated tau protein, LOD = limit of detection, LP = lumboperitoneal, MMSE = Mini-Mental State Examination, VP = ventriculoperitoneal, amyloid-β, hydrocephalus, iNPH, iNPH = idiopathic normal pressure hydrocephalus
National Category
Neurology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-342227 (URN)10.3171/2017.7.JNS171005 (DOI)000454604000014 ()29350601 (PubMedID)
Funder
The Swedish Brain Foundation
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2019-12-06Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6249-569x

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