scholarly journals Dense core vesicle markers in CSF and cortical tissues of patients with Alzheimer’s disease

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Neus Barranco ◽  
Virginia Plá ◽  
Daniel Alcolea ◽  
Irene Sánchez-Domínguez ◽  
Reiner Fischer-Colbrie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dense Core ◽  
University Hospital ◽  
Secretory Proteins ◽  
Dense Core Vesicle ◽  
Therapeutic Trial ◽  
Strongly Correlated ◽  
Granulovacuolar Degeneration ◽  
Prohormone Convertases

Abstract Background New fluid biomarkers for Alzheimer's disease (AD) that reveal synaptic and neural network dysfunctions are needed for clinical practice and therapeutic trial design. Dense core vesicle (DCV) cargos are promising cerebrospinal fluid (CSF) indicators of synaptic failure in AD patients. However, their value as biomarkers has not yet been determined. Methods Immunoassays were performed to analyze the secretory proteins prohormone convertases PC1/3 and PC2, carboxypeptidase E (CPE), secretogranins SgIII and SgII, and Cystatin C in the cerebral cortex (n = 45, provided by Bellvitge University Hospital) and CSF samples (n = 66, provided by The Sant Pau Initiative on Neurodegeneration cohort) from AD patients (n = 56) and age-matched controls (n = 55). Results In AD tissues, most DCV proteins were aberrantly accumulated in dystrophic neurites and activated astrocytes, whereas PC1/3, PC2 and CPE were also specifically accumulated in hippocampal granulovacuolar degeneration bodies. AD individuals displayed an overall decline of secretory proteins in the CSF. Interestingly, in AD patients, the CSF levels of prohormone convertases strongly correlated inversely with those of neurodegeneration markers and directly with cognitive impairment status. Conclusions These results demonstrate marked alterations of neuronal-specific prohormone convertases in CSF and cortical tissues of AD patients. The neuronal DCV cargos are biomarker candidates for synaptic dysfunction and neurodegeneration in AD.

The active form of glycogen synthase kinase-3? is associated with granulovacuolar degeneration in neurons in Alzheimer's disease

2002 ◽  
Vol 103 (2) ◽  
pp. 91-99 ◽  
Author(s):  
Allal Boutajangout ◽  
Karelle Leroy ◽  
Authelet M. ◽  
Brian Anderton ◽  
Jean-Pierre Brion ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Active Form ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Granulovacuolar Degeneration

scholarly journals Diminished O-GlcNAcylation in Alzheimer's disease is strongly correlated with mitochondrial anomalies

2019 ◽  
Vol 1865 (8) ◽  
pp. 2048-2059 ◽  
Author(s):  
Tiffany S. Pinho ◽  
Sónia C. Correia ◽  
George Perry ◽  
António Francisco Ambrósio ◽  
Paula I. Moreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Strongly Correlated ◽  
Mitochondrial Anomalies

Incidence of head injury and traumatic brain injury among people with Alzheimer’s disease

2019 ◽  
Vol 73 (5) ◽  
pp. 451-454 ◽  
Author(s):  
Sarianna Ilmaniemi ◽  
Heidi Taipale ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
Sirpa Hartikainen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Head Injuries ◽  
Community Dwelling ◽  
University Hospital ◽  
Health Concern ◽  
Increased Risk

BackgroundInjuries caused by falling are a major health concern among older population. For older people, falls are the leading cause of head injuries; especially, persons with cognitive disorders have an increased risk of falling.ObjectiveTo compare the incidence of head injury and traumatic brain injury (TBI) among persons with Alzheimer’s disease (AD) with persons without AD.MethodsThis register-based study was conducted on a nationwide cohort, which includes all community-dwelling persons diagnosed with AD in Finland in 2005–2011. Persons with previous head injuries were excluded, leaving 67 172 persons with AD. For each person with AD, a matching person without AD and previous head injury were identified with respect to age, sex and university hospital district. The Cox proportional hazard model and competing risk analyses were used to estimate HR for head injury and TBI.ResultsPersons with AD had 1.34-fold (95% CI 1.29 to 1.40) risk of head injuries and 1.49-fold (95% CI 1.40 to 1.59) risk of TBIs after accounting for competing risks of death and full adjustment by socioeconomic status, drug use and comorbidities.ConclusionPersons with AD are more likely to have a head injury or TBI incident than persons without AD.

scholarly journals Dense-Core Plaques in Tg2576 and PSAPP Mouse Models of Alzheimer's Disease Are Centered on Vessel Walls

2005 ◽  
Vol 167 (2) ◽  
pp. 527-543 ◽  
Author(s):  
Samir Kumar-Singh ◽  
Daniel Pirici ◽  
Eileen McGowan ◽  
Sally Serneels ◽  
Chantal Ceuterick ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Dense Core ◽  
Vessel Walls

scholarly journals Decreased salivary lactoferrin levels are specific to Alzheimer’s disease

2020 ◽  
Author(s):  
Marta González-Sánchez ◽  
Fernando Bartolome ◽  
Desiree Antequera ◽  
Veronica Puertas-Martín ◽  
Pilar González ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Diagnostic Performance ◽  
Group Versus ◽  
Amyloid Β ◽  
University Hospital ◽  
Control Group ◽  
Amyloid Pet ◽  
Prodromal Ad ◽  
Study Participants

Abstract Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary levels of Lf in AD patients, one of the major antimicrobial peptides. Methods To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Study participants for cohort 1 (n = 116) were enrolled from the 12 de Octubre University Hospital Neurology Service in Madrid (Spain) and Pablo de Olavide University in Sevilla (Spain). Study participants for cohort 2 (n = 142) were enrolled as part of the Atherobrain - Heart to Head (H2H) project. Participants underwent neurological and neuropsychological examination, saliva sampling, and amyloid-Positron-Emission Tomography (PET) neuroimaging. Results The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET + ) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (95% CI 0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from other dementias as FTD with over 87% sensitivity and 91% specificity. Conclusion Therefore, salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.

scholarly journals Narrativity Analysis in Alzheimer’s Disease

2018 ◽  
Author(s):  
P Thomas ◽  
R Billon ◽  
C Hazif-Thomas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Language Impairment ◽  
Neuropsychological Tests ◽  
Memory Impairment ◽  
Regression Coefficient ◽  
University Hospital ◽  
Sociodemographic Data ◽  
Pls Analysis ◽  
Fluency Test

Context. Alzheimer’s Disease (AD) is a neurodegenerative illness with frequency of occurrence increasing with old age. If memory impairment setting progressively in is here an element associated upfront, other neurocognitive troubles are also associated, for example, language impairment which can degenerate into aphasia. Aim of the study. To evaluate semantic and textual impairment in AD. Methods. Populationsstudied concerned 151 AD patients in consultation at Brest University Hospital. Certain sociodemographic data (sex, age, cultural levels) were collected as well as results from neuropsychological tests: (Folstein – MMSE; Dubois’s 5-word test; fluencies, Dubois’ s frontal test battery; Cornell’s scale for depression; Barbizet’s test, “The Lion’s tale”, for textual analysis. Demented patients were composed of 102 females and 49 males of average age 80.3 ± 6.91. All the tests, including the number of items memorized latterly in the Barbizet’s test are impaired all the more by Folstein’s test being altered. The formal fluency on demented patients is less impaired than the semantical lexical fluency test (scored respectively 5.74 ± 1. 09 versus 4.41 ± 2. 19;t= 5.60, p<0.01). The studied demented cohort shows more intrusions (n=36) than inversions in the delayed Lion’s tale, whether for items or for episodes in which they occur (n=19). The regressive PLS analysis shows that for the explanation of the overall scores to do with “The lion’s tale”, calculated later, only attainment of lexical fluency has any notable influence (Regression coefficient CR=0.224) or, more accessorily, the cultural level (CR=0.12). Conclusions. Attainment of category fluency and patient culture levels have effects on narrativity. Keywords: Alzheimer’s Disease, semiotics, semantics, textuality

scholarly journals Necrosome complex detected in granulovacuolar degeneration is associated with neuronal loss in Alzheimer’s disease

2019 ◽  
Vol 139 (3) ◽  
pp. 463-484 ◽  
Author(s):  
Marta J. Koper ◽  
Evelien Van Schoor ◽  
Simona Ospitalieri ◽  
Rik Vandenberghe ◽  
Mathieu Vandenbulcke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Loss ◽  
Granulovacuolar Degeneration

scholarly journals Quantitative Measurement of Cerebrospinal Fluid Amyloid-β Species by Mass Spectrometry

2020 ◽  
pp. 1-12
Author(s):  
Yusuke Seino ◽  
Takumi Nakamura ◽  
Tomoo Harada ◽  
Naoko Nakahata ◽  
Takeshi Kawarabayashi ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Quantitative Measurement ◽  
Amyloid Β ◽  
High Sensitivity ◽  
Csf Biomarkers ◽  
Strongly Correlated ◽  
Csf Levels

Background: High sensitivity liquid chromatography mass spectrometry (LC-MS/MS) was recently introduced to measure amyloid-β (Aβ) species, allowing for a simultaneous assay that is superior to ELISA, which requires more assay steps with multiple antibodies. Objective: We validated the Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 assay by LC-MS/MS and compared it with ELISA using cerebrospinal fluid (CSF) samples to investigate its feasibility for clinical application. Methods: CSF samples from 120 subjects [8 Alzheimer’s disease (AD) with dementia (ADD), 2 mild cognitive dementia due to Alzheimer’s disease (ADMCI), 14 cognitively unimpaired (CU), and 96 neurological disease subjects] were analyzed. Aβ species were separated using the Shimadzu Nexera X2 system and quantitated using a Qtrap 5500 LC-MS/MS system. Aβ1-40 and Aβ1-42 levels were validated using ELISA. Results: CSF levels in CU were 666±249 pmol/L in Aβ1-38, 2199±725 pmol/L in Aβ1-40, 153.7±79.7 pmol/L in Aβ1-42, and 9.78±4.58 pmol/L in Aβ1-43. The ratio of the amounts of Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 was approximately 68:225:16:1. Linear regression analyses showed correlations among the respective Aβ species. Both Aβ1-40 and Aβ1-42 values were strongly correlated with ELISA measurements. No significant differences were observed in Aβ1-38 or Aβ1-40 levels between AD and CU. Aβ1-42 and Aβ1-43 levels were significantly lower, whereas the Aβ1-38/1-42, Aβ1-38/1-43, and Aβ1-40/Aβ1-43 ratios were significantly higher in AD than in CU. The basic assay profiles of the respective Aβ species were adequate for clinical usage. Conclusion: A quantitative LC-MS/MS assay of CSF Aβ species is as reliable as specific ELISA for clinical evaluation of CSF biomarkers for AD.

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