scholarly journals In vivo Characterization of Biochemical Variants of Amyloid-β in Subjects with Idiopathic Normal Pressure Hydrocephalus and Alzheimer’s Disease Neuropathological Change

2021 ◽  
pp. 1-10
Author(s):  
Sylwia Libard ◽  
Jochen Walter ◽  
Irina Alafuzoff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Normal Pressure Hydrocephalus ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Neuropathological Change ◽  
The Brain

Background: Stepwise occurrence of biochemically modified amyloid-β (Aβ) in the brain of subjects with Alzheimer’s disease (AD) has been suggested to be of significance for cognitive impairment. Our previous reports have shown that Aβ is observed in 63% of all subjects with idiopathic normal pressure hydrocephalus (iNPH) suggesting that the majority of iNPH subjects with Aβ are indeed also suffering from AD. Objective: We assessed the occurrence of biochemically modified Aβ variants, in vivo, in subjects with iNPH and in a cohort of postmortem brain samples from patients with dementia. Methods: We assessed Aβ proteins in 127 diagnostic brain biopsies obtained from subjects with iNPH and in a cohort of subjects with dementia by means of immunohistochemistry. Results: The pyroglutamylated Aβ (pyAβ) precedes the aggregation of phosphorylated Aβ (pAβ) during the AD neuropathological change progression; moreover, these modified variants of Aβ correlate with hyperphosphorylated tau in the frontal cortical area of human brain. Our results confirm the existence of the suggested biochemical stages of Aβ aggregation that might be of significance for neurodegeneration leading to cognitive impairment. Conclusion: The observation that both pyAβ and pAβ are seen in vivo in iNPH subjects is intriguing. It has been reported that most of the iNPH subjects with Aβ in the brain biopsy indeed develop AD with time. Based on our current and previous results, it is clinically merited to obtain a diagnostic biopsy from a subject with iNPH. When Aβ is observed in the biopsy, the biochemical characterization is of interest.

scholarly journals CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

2019 ◽  
Vol 90 (10) ◽  
pp. 1117-1123 ◽  
Author(s):  
Anna Jeppsson ◽  
Carsten Wikkelsö ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Radu Constantinescu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Normal Pressure Hydrocephalus ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Prediction Algorithm ◽  
Csf Biomarkers ◽  
T Tau

ObjectiveTo examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer’s disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders.MethodsThe study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson’s disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer’s disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1).ResultsPatients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers.ConclusionsThe combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.

scholarly journals Elevated CSF LRG and Decreased Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Vol 10 (5) ◽  
pp. 1105
Author(s):  
Aleksi Vanninen ◽  
Madoka Nakajima ◽  
Masakazu Miyajima ◽  
Tuomas Rauramaa ◽  
Merja Kokki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Normal Pressure Hydrocephalus ◽  
Brain Biopsy ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Potential Biomarker ◽  
Shunt Response ◽  
T Tau ◽  
The Brain

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer’s disease (AD) pathology among the iNPH patients. CSF LRG, Aβ1-42, P-tau181, and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p < 0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., Aβ1-42, T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls (<0.001). Our findings support that the LRG levels in the CSF are potentially useful for the diagnostics of iNPH, independent of the brain AD pathology, but contrary to previous findings, not for predicting the shunt response. Our findings also suggest a need for specific reference values of the CSF AD biomarkers for the diagnostics of comorbid AD pathology in the iNPH patients.

Idiopathic normal pressure hydrocephalus and Alzheimer's disease in clinical practice: comorbidity and differentiation

2020 ◽  
pp. 36-43
Author(s):  
V. Yu. Lobzin ◽  
M. R.o. Alizade ◽  
A. V. Lapina ◽  
S. V. Lobzin ◽  
K. A. Kolmakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Brain Parenchyma ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Protein Biomarkers ◽  
Brain Functions

The idiopathic normal pressure hydrocephalus (Hakim – Adams syndrome) is characterized by the expansion of cerebrospinal cavities, which is clinically manifested by triad symptoms: cognitive impairment, impaired gait and urination. In this research the severity and modality of cognitive impairment, the pattern of gait changes and the levels of protein biomarkers of amyloidosis and neurodegeneration and neuroimaging changes was evaluated for idiopathic normal pressure hydrocephalus, Alzheimer's disease and their combination. It has been established that for patients with idiopathic normal pressure hydrocephalus the most characteristic is the dysregulatory type of disorders of higher brain functions, while for patients with a combination of Alzheimer's disease and idiopathic normal pressure hydrocephalus, mnemonic disorders are also detected. The specific changes of cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus are higher levels of amyloid beta, a decrease concentration of tau and phosphorylated tau-protein compared to patients with Alzheimer's disease. In the case of a combination of diseases (comorbidity), it was characterized by intermediate results by cerebrospinal fluid biomarkers. We also revealed patterns of transformation of moderate cognitive impairment into dementia (according to the ratio of tau/Aβ‑42 and ftau /Aβ‑42). The value of evaluating the results of magnetic resonance imaging using special techniques that evaluate both the expansion of the ventricular system and atrophy of the brain parenchyma. Comorbid patients are characterized by a combination of these processes based on the results of neuroimaging. That is why it is necessary to use complex visually analog neuroimaging scales for differential diagnosis and establishing diagnosis. Also, in the course of this work, an algorithm is proposed for mandatory clinical-neuropsychological and laboratory-instrumental examination of patients with cognitive impairment in idiopathic normal pressure hydrocephalus, Alzheimer's disease and their combination.

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