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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
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
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: 2019-01-28Bibliographically approved
Rauramaa, T., Saxlin, A., Lohvansuu, K., Alafuzoff, I., Pitkanen, A. & Soininen, H. (2018). Epilepsy in neuropathologically verified Alzheimer's disease. Seizure, 58, 9-12
Open this publication in new window or tab >>Epilepsy in neuropathologically verified Alzheimer's disease
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2018 (English)In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 58, p. 9-12Article in journal (Refereed) Published
Abstract [en]

Purpose: Subjects with Alzheimer's disease (AD) have been shown to be at a higher risk for epilepsy. The vast majority of the previous studies have not included a full neuropathological examination. Methods: The objective of this study was to assess the prevalence of epilepsy and clinicopathological characteristics in a well-defined study group of 64 subjects with AD. We evaluated the clinicopathological findings in 64 subjects (mean age at death 85 +/- 8.6 years) from a longitudi-nal study cohort of patients with dementia. Results: Eleven out of the 64 subjects (17%) had a history of epilepsy, which is comparable to previous studies. The subjects with AD and epilepsy were significantly younger at the time of AD diagnosis and at the time of hospitalisation. In addition, their duration of AD was longer. Concomitant neuropathology in addition to AD was common in both groups and the ApoE genotypes did not differ significantly between the groups. Conclusion: The strength of this study is a thorough neuropathological examination of all study subjects. Our findings support the previous literature regarding the prevalence of epilepsy in subjects with AD. We have shown that the subjects with AD and epilepsy differ significantly from the subjects without epilepsy.

Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2018
Keywords
Alzheimer, Dementia, Epilepsy, Autopsy, Neurodegeneration
National Category
Neurology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-360996 (URN)10.1016/j.seizure.2018.03.014 (DOI)000436884500003 ()29602145 (PubMedID)
Available from: 2018-09-26 Created: 2018-09-26 Last updated: 2019-01-07Bibliographically approved
Pyykko, O. T., Nerg, O., Niskasaari, H.-M., Niskasaari, T., Koivisto, A. M., Hiltunen, M., . . . Leinonen, V. (2018). Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure Hydrocephalus. World Neurosurgery, 112, E624-E631
Open this publication in new window or tab >>Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure Hydrocephalus
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2018 (English)In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 112, p. E624-E631Article in journal (Refereed) Published
Abstract [en]

OBJECT: To investigate the incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring, with a brain biopsy specimen immunostained against amyloid-beta and hyper-phosphorylated tau. Hospital records were reviewed for vascular diseases and type 2 diabetes mellitus (T2DM). Death certificates and yearly population of the catchment area were obtained from national registries. RESULTS: A total of 283 patients had a clinical diagnosis of iNPH, leading to a median annual incidence of 1.58 iNPH patients per 100,000 inhabitants (range, 0.8-4.5). Alzeimer disease-related brain biopsy findings were less frequent in iNPH patients than in non-iNPH patients (P < 0.05). An overrepresentation of hypertension (52% vs. 33%, P < 0.001) and T2DM (23% vs. 13%, P = 0.002) was noted in iNPH patients. Age (hazard ratio [HR] 1.04/year, 95% confidence interval [CI] 1.03-1.06, P< 0.001) and T2DM (HR 1.63, 95% CI 1.23-2.16, P < 0.001) increased the risk of death in the iNPH patients and in the total population. iNPH was associated with decreased risk of death (HR 0.63, 95% CI 0.50-0.78, P < 0.001). The most frequent causes of death were cardiovascular and cerebrovascular disease. Dementia as a cause of death was more common in non-iNPH patients (27% vs. 10%, P < 0.001). CONCLUSIONS: Hypertension and T2DM are common in iNPH and the latter causes excess mortality in the affected patients.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
Keywords
Cause of death, Comorbidity, Incidence, Mortality, Normal pressure hydrocephalus, Survival
National Category
Neurology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-356808 (URN)10.1016/j.wneu.2018.01.107 (DOI)000432932700074 ()29374607 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2019-01-07Bibliographically approved
Alafuzoff, I. (2018). Minimal neuropathologic diagnosis for brain banking in the normal middle-aged and aged brain and in neurodegenerative disorders.. Handbook of Clinical Neurology, 150, 131-141, Article ID B978-0-444-63639-3.00010-4.
Open this publication in new window or tab >>Minimal neuropathologic diagnosis for brain banking in the normal middle-aged and aged brain and in neurodegenerative disorders.
2018 (English)In: Handbook of Clinical Neurology, ISSN 0072-9752, E-ISSN 2212-4152, Vol. 150, p. 131-141, article id B978-0-444-63639-3.00010-4Article in journal (Refereed) Published
Abstract [en]

Research on human brain diseases is currently often conducted on cell cultures and animals. Several questions however can only be addressed by studying human postmortem brain tissue. However, brain tissue obtained postmortem almost always displays pathology that is often related to the aging phenomenon. Thus, in order to be certain that the answers obtained are reliable, a systematic and thorough assessment of the brain tissue to be studied should be carried out. We are currently aware of several protein alterations that are found in middle-aged and aged brains that are obtained from neurologically unimpaired subjects. The most common alteration is hyperphosphorylation of τ, observed in both neurons and glial cells, in certain brain regions, followed by β-amyloid aggregation in the neuropil and vessel walls. Less common protein alterations are those noted for α-synuclein and Tar DNA-binding protein 43. It is noteworthy that these alterations, when found in excess, are diagnostic for various neurodegenerative diseases, such as Alzheimer disease, Pick disease, progressive supranuclear palsy, corticobasal degeneration, Parkinson disease, Lewy body dementia, and frontotemporal lobar degeneration. Since 1990, the neuropathology community has been aware that these protein alterations tend to progress in an orderly neuroanatomically defined manner and have thus designed a method to define a stage or a phase of the protein alteration. The neuropathology community has defined an initiation site, or neuroanatomic area that they presume the alteration originates from, and defined a presumed pattern of progression from the initiation site to other brain areas. Thus a reliable and reproducible description of each case regarding these alterations can be achieved. In addition to the above alterations, the brain tissue is also prone to various vascular alterations that should be registered as seen or not seen even if the significance of these alterations is still unclear.

Keywords
histology, hyperphosphorylated t, immunohistochemistry, regional distribution, sampling, staging, transactive DNA binding protein 43, α-synuclein, β-amyloid
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372553 (URN)10.1016/B978-0-444-63639-3.00010-4 (DOI)29496136 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-05-22Bibliographically approved
Libard, S., Laurell, K., Cesarini, K. G. & Alafuzoff, I. (2018). Progression of Alzheimer's Disease-Related Pathology and Cell Counts in a Patient with Idiopathic Normal Pressure Hydrocephalus. Journal of Alzheimer's Disease, 61(4), 1451-1461
Open this publication in new window or tab >>Progression of Alzheimer's Disease-Related Pathology and Cell Counts in a Patient with Idiopathic Normal Pressure Hydrocephalus
2018 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, no 4, p. 1451-1461Article in journal (Refereed) Published
Abstract [en]

We had an opportunity to assess the change observed in the brain regarding Alzheimer’s disease (AD)-related alterations, cell count, and inflammation that took place during a period of 21 months in a subject with a definite diagnosis of AD and idiopathic Normal Pressure Hydrocephalus (iNPH). Four neuronal markers, i.e., synaptophysin, microtubule associated protein 2, non-phosphorylated neurofilament H (SMI32), and embryonic lethal abnormal visual system proteins 3/4 HuC/HuD (HuC/HuD); three microglial markers CD68, Human Leucocytic Antigen DR, ionized calcium-binding adaptor molecule 1, glial fibrillary acidic protein (GFAP); and AD-related markers, hyperphosphorylated τ (HPτ) and amyloid-β (Aβ, Aβ40, Aβ42) were assessed. Morphometrically assessed immunoreactivity of all neuronal and all microglial markers and Aβ42 decreased parallel with an increase in the HPτ in the frontal cortex. The expression of GFAP was stable with time. The first sample was obtained during the therapeutic shunting procedure for iNPH, and the second sample was obtained postmortem. Negligible reactive changes were observed surrounding the shunt channel. In conclusion, in the late stage of AD with time, a neuronal loss, increase in the HPτ, and decrease in Aβ42 and microglia was observed, whereas the expression of GFAP was rather stable. The observations described here suggest that when a brain biopsy has been obtained from an adult subject with iNPH, the assessment of postmortem brain is of major significance.

Keywords
Amyloid-beta, astrocytes, hyperphosphorylated tau, idiopathic normal pressure hydrocephalus, immunohistochemistry, microglia, neurons
National Category
Neurosciences Neurology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-346377 (URN)10.3233/JAD-170446 (DOI)000423364400018 ()29376849 (PubMedID)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2019-01-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6249-569x

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