scholarly journals Interleukinų IL1A ir IL6 genų polimorfizmas: sąsajų su APOE genotipu ir sporadinės Alzheimerio ligos klinikine eiga paieška Interleukin IL1a and IL6 gene polymorphism: search for association with APOE genotype and clinical course of sporadic Alzheimer’s disease

2020 ◽  
Vol 23 (81) ◽  
pp. 130-139
Author(s):  
G. Pšemeneckienė ◽  
K. Petrikonis ◽  
D. Rastenytė
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Clinical Course ◽  
Apoe Genotype ◽  
Sporadic Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Il6 Gene

Įvadas. Yra duomenų, kad IL1α ir IL6, kaip vienų svarbiausių citokinų, dalyvaujančių neurouždegimo procesuose, genų polimorfizmai yra susiję su Alzheimerio ligos (AL) rizika. Šiame tyrime siekėme įvertinti IL1A -889C>T ir IL6 -174G>C polimorfizmų sąsajas su sporadinės AL rizika APOE ε4 nešiotojams ir APOE rizikos alelio neturintiems asmenims. Taip pat tyrėme IL1A -889C>T ir IL6 -174G>C polimorfizmų sąsajas su AL progresavimo pobūdžiu. Tiriamieji ir tyrimo metodai. Tyrime dalyvavo 110 sergančiųjų sporadine AL ir 115 sutapatintų pagal amžių ir lytį sveikų kontrolinių tiriamųjų, kurių pažinimo funkcijos nesutrikusios (Lietuvos populiacija). IL1A -889C>T (rs1800587) ir IL6 -174G>C (rs1800795, Intro- no tipo) genotipavimas atliktas tikro laiko PGR (TL-PGR) metodu. Rezultatai. IL1A -889C>T genotipų dažniai APOE4+ grupėje (C/C – 52,9 %, C/T – 41,2 %, T/T – 5,9 %), lyginant su APOE4- sergančiaisiais AL (C/C – 55,6 %, C/T – 37,0 %, T/T – 7,4 %), nesiskyrė (p = 0,887). Sergantiems AL pacientams IL6 -174G>C genotipai APOE4+ grupėje (G/G – 11,8 %, G/C – 62,7 %, C/C – 25,5 %) ir APOE4- grupėje (G/G – 14,8 %, G/C – 61,1 %, C/C – 24,1 %) buvo pasiskirstę panašiai (p = 0,898). Genotipų dažniai reikšmingai nesiskyrė sergantiesiems greitai progresuojančia AL, lyginant su lėtai progresuojančia AL (p (IL1A -889C>T) = 0,638; p (IL6 -174G>C) = 0,118). IL1A -889C>T ir IL6 -174G>C polimorfizmų paveldėjimas (dominantinio, overdominantinio ir recesyvinio modeli0), atsižvelgiant į APOE genotipą, reikšmingai nekeitė galimybių santykio sirgti AL (p < 0,05). Lėtai ir greitai progresuojančios AL grupėse IL1A -889C>T ir IL6 -174G>C polimorfizmų paveldėjimas AL galimybei reikšmingos įtakos neturėjo (p < 0,05). Išvados. IL1A -889C>T ir IL6 -174G>C genotipų pasiskirstymas grupėse pagal APOE ε4 ir grupėse pagal AL progresavimo pobūdį reikšmingai nesiskyrė. Reikšmingų IL1A -889C>T ir IL6 -174G>C polimorfizmų sąsajų su AL rizika nei APOE4+, nei APOE4- tiriamiesiems nenustatyta. Mūsų duomenimis, IL1A -889C>T ir IL6 -174G>C polimorfizmų paveldėjimas nesusijęs su spartesniu AL progresavimu.

scholarly journals Decline in verbal memory during preclinical Alzheimer's disease: Examination of the effect of APOE genotype

2002 ◽  
Vol 8 (7) ◽  
pp. 943-955 ◽  
Author(s):  
KELLY L. LANGE ◽  
MARK W. BONDI ◽  
DAVID P. SALMON ◽  
DOUGLAS GALASKO ◽  
DEAN C. DELIS ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Episodic Memory ◽  
Verbal Memory ◽  
Verbal Learning ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Dementia Syndrome ◽  
Ε4 Allele

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-ε4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE ε4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale–Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-ε4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD. (JINS, 2002, 8, 943–955.)

Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease

2018 ◽  
Vol 15 (10) ◽  
pp. 938-950 ◽  
Author(s):  
Martina Zverova ◽  
Eva Kitzlerova ◽  
Zdenek Fisar ◽  
Roman Jirak ◽  
Jana Hroudova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Apoe Genotype ◽  
Plasma Biomarkers ◽  
Plasma Melatonin ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Severity Of Dementia

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. Objective: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. Method: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. Results: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. Conclusion: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.

scholarly journals The APOE ε4/ε4 Genotype Potentiates Vascular Fibrin(Ogen) Deposition in Amyloid-Laden Vessels in the Brains of Alzheimer's Disease Patients

2013 ◽  
Vol 33 (8) ◽  
pp. 1251-1258 ◽  
Author(s):  
Karin Hultman ◽  
Sidney Strickland ◽  
Erin H Norris
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Role ◽  
Apoe Genotype ◽  
Postmortem Brain ◽  
Amyloid Angiopathy ◽  
Apoe Ε4 ◽  
Cerebrovascular Dysfunction ◽  
Postmortem Brain Tissue ◽  
Clotting Protein

Evidence indicates a critical role for cerebrovascular dysfunction in Alzheimer's disease (AD) pathophysiology. We have shown that fibrin(ogen), the principal blood-clotting protein, is deposited in the AD neurovasculature and interacts with beta-amyloid (Ab), resulting in increased formation of blood clots. As apolipoprotein E (ApoE), a lipid-transporting protein with three human isoforms (E2, E3, and E4), also binds to Aβ, we hypothesized that ApoE and fibrin(ogen) may have a combined effect on the vascular pathophysiology in AD. We assessed whether APOE genotype differentially influences vascular fibrin(ogen) deposition in postmortem brain tissue using immunohistochemistry. An increased deposition of fibrin(ogen) was observed in AD cases compared with non-demented controls, and there was a strong correlation between cerebral amyloid angiopathy (CAA) severity and fibrin(ogen) deposition. Moreover, brains from AD cases homozygous for APOE ε4 showed increased deposition of fibrin(ogen), specifically in CAA- and oligomeric Aβ-positive vessels compared with AD APOE ε2 and ε3 allele carriers, an effect that was not directly linked to CAA severity and cerebrovascular atherosclerosis. These data further support a role for fibrin(ogen) in AD pathophysiology and link the APOE ε4/ε4 genotype with increased thrombosis and/or impaired fibrinolysis in the human AD brain.

scholarly journals P4-573: PROXIMITY TO PARENTAL ONSET AND APOE ε4 INDEPENDENTLY CONTRIBUTE TO AMYLOID BURDEN IN MIDDLE-AGED ADULTS WITH A FAMILY HISTORY OF SPORADIC ALZHEIMER'S DISEASE

2019 ◽  
Vol 15 ◽  
pp. P1539-P1539
Author(s):  
Eider M. Arenaza-Urquijo ◽  
Gemma Salvadó ◽  
Carolina Minguillón ◽  
Marta Crous-Bou ◽  
Gonzalo Sánchez-Benavides ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Amyloid Burden ◽  
Middle Aged ◽  
Sporadic Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
History Of ◽  
Middle Aged Adults

The Application Value of ApoE Gene Polymorphism in Alzheimer's Disease

2019 ◽  
Vol 9 (10) ◽  
pp. 1403-1407
Author(s):  
Cong Chen ◽  
Yuhui Zhang ◽  
Bin Chen ◽  
Chaosheng Zeng ◽  
Min Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Apoe Genotype ◽  
Apoe Gene ◽  
Control Group ◽  
Apolipoprotein E Polymorphism ◽  
Abnormal Lipid Metabolism ◽  
And Control ◽  
Apoe Gene Polymorphism

To explore the association of apolipoprotein E polymorphism with Alzheimer's disease (AD), so as to provide possible research value for potential targeted therapy. 120 AD patients and 50 healthy volunteers were enrolled to extract fasting blood samples. ApoE gene polymorphism and blood lipids were tested in blood. ApoE gene and genotype frequency between AD group and control group were compared by PCR and sequencing methods. MMSE, CDR, and BPSD were used to determine the intelligence. ApoE genotype was detected by DNA microarray. ɛ4 carrier accounted for 45% in AD group, which was significantly elevated compared with control group (12%) (P < 0.05). TG, TC, and LDL-C levels were increased, while HDL-C was reduced in ɛ4 allele carriers (allP < 0.05). The MMSE scores of ApoEɛ4 genotype carriers in AD group were markedly lower than those of nonApoEɛ4 genotype carriers (P < 0.05) and control (P < 0.01). The proportion of dementia in ApoEɛ4 genotype carriers from AD group was apparently higher than the ɛ4 gene non-carriers (P < 0.05). The ApoEɛ4 gene is an AD risk factor. The changes of genotype and frequency of ApoEɛ4 gene are the main factors leading to abnormal lipid metabolism in AD patients, suggesting that ApoEɛ4 gene detection might be helpful for the early diagnosis and treatment of AD.

Capillary cerebral amyloid angiopathy identifies a distinct APOE ε4-associated subtype of sporadic Alzheimer’s disease

2010 ◽  
Vol 120 (2) ◽  
pp. 169-183 ◽  
Author(s):  
Dietmar Rudolf Thal ◽  
Andreas Papassotiropoulos ◽  
Takaomi C. Saido ◽  
W. Sue T. Griffin ◽  
Robert E. Mrak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Sporadic Alzheimer’S Disease ◽  
Apoe Ε4 ◽  
Cerebral Amyloid

Interleukin 6-174 G/C promoter gene polymorphism and sporadic Alzheimer's disease: geographic allele and genotype variations in Europe

2004 ◽  
Vol 39 (10) ◽  
pp. 1567-1573 ◽  
Author(s):  
Cristiano Capurso ◽  
Vincenzo Solfrizzi ◽  
Alessia D'Introno ◽  
Anna M. Colacicco ◽  
Sabrina A. Capurso ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Interleukin 6 ◽  
Sporadic Alzheimer’S Disease ◽  
Promoter Gene

scholarly journals The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype

2020 ◽  
Vol 17 (7) ◽  
pp. 667-679
Author(s):  
Matteo De Marco ◽  
Riccardo Manca ◽  
Janine Kirby ◽  
Guillaume M. Hautbergue ◽  
Daniel J. Blackburn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Functioning ◽  
Grey Matter ◽  
Linear Models ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Allele Status ◽  
Ε4 Allele ◽  
Clinical Profiles

Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers. Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants. Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.

scholarly journals Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease

2018 ◽  
Vol 15 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Winnie Qian ◽  
Corinne E. Fischer ◽  
Tom A. Schweizer ◽  
David G. Munoz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apoe Genotype ◽  
Lewy Bodies ◽  
Functional Impairments ◽  
Significant Interaction Effect ◽  
Functional Activities ◽  
Apoe Ε4 ◽  
Lewy Body Pathology ◽  
Ε4 Allele

Background: Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ε4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear. Objective: We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ε4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ε4, Lewy bodies, and psychosis. Methods: Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ε4, as well as their interaction. Results: Psychosis and the presence of APOE ε4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ε4 on MMSE scores, with APOE ε4 negatively affecting patients with hallucinations-only psychosis. APOE ε4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. Conclusion: Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ε4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ε4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.

Lack of association between MnSOD gene polymorphism and sporadic Alzheimer’s Disease

2005 ◽  
Vol 17 (6) ◽  
pp. 445-448 ◽  
Author(s):  
Mariacarla Ventriglia ◽  
Luisella Bocchio Chiavetto ◽  
Catia Scassellati ◽  
Rosanna Squitti ◽  
Giuliano Binetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Sporadic Alzheimer’S Disease ◽  
Mnsod Gene
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