Predicting Alzheimer's disease with practice effects, APOE genotype and brain metabolism

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

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Breast Cancer, Alzheimer’s Disease, and APOE4 Allele in the UK Biobank Cohort

Journal of Alzheimer s Disease Reports ◽

10.3233/adr-200266 ◽

2021 ◽

Vol 5 (1) ◽

pp. 49-53

Author(s):

Steven Lehrer ◽

Peter H. Rheinstein

Keyword(s):

Breast Cancer ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apoe Genotype ◽

Uk Biobank ◽

Breast Cancer Patients ◽

Apoe4 Allele ◽

Significant Difference ◽

The Uk ◽

Cognitive Problems

Background: Cognitive problems are common in breast cancer patients. The apolipoprotein E4 (APOE4) gene, a risk factor for Alzheimer’s disease (AD), may be associated with cancer-related cognitive decline. Objective: To further evaluate the effects of the APOE4 allele, we studied a cohort of patients from the UK Biobank (UKB) who had breast cancer; some also had AD. Methods: Our analysis included all subjects with invasive breast cancer. Single nucleotide polymorphism (SNP) data for rs 429358 and rs 7412 was used to determine APOE genotypes. Cognitive function as numeric memory was assessed with an online test (UKB data field 20240). Results: We analyzed data from 2,876 women with breast cancer. Of the breast cancer subjects, 585 (20%) carried the APOE4 allele. Numeric memory scores were significantly lower in APOE4 carriers and APOE4 homozygotes than non-carriers (p = 0.046). 34 breast cancer subjects (1.1%) had AD. There was no significant difference in survival among genotypes ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4. Conclusion: UKB data suggest that cognitive problems in women with breast cancer are, for the most part, mild, compared with other sequelae of the disease. AD, the worst cognitive problem, is relatively rare (1.1%) and, when it occurs, APOE genotype has little impact on survival.

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ApoE genotype and familial Alzheimer's disease: a possible influence on age of onset in APP717 Val → Ile mutated families

Neuroscience Letters ◽

10.1016/0304-3940(94)11100-w ◽

1995 ◽

Vol 183 (1-2) ◽

pp. 1-3 ◽

Cited By ~ 30

Author(s):

Benedetta Nacmias ◽

Stefania Latorraca ◽

Patrizia Piersanti ◽

Paolo Forleo ◽

Silvia Piacentini ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Age Of Onset ◽

Apoe Genotype ◽

Familial Alzheimer’S Disease ◽

Familial Alzheimer's Disease

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Executive deficits and regional brain metabolism in Alzheimer's disease

International Journal of Geriatric Psychiatry ◽

10.1002/gps.2452 ◽

2010 ◽

Vol 25 (11) ◽

pp. 1150-1158 ◽

Cited By ~ 28

Author(s):

Benjamin K. P. Woo ◽

Dylan G. Harwood ◽

Rebecca J. Melrose ◽

Mark A. Mandelkern ◽

Olivia M. Campa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Metabolism ◽

Regional Brain ◽

Executive Deficits

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

Journal of the International Neuropsychological Society ◽

10.1017/s1355617702870096 ◽

2002 ◽

Vol 8 (7) ◽

pp. 943-955 ◽

Cited By ~ 65

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.)

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O2-04-05: Relationships between hippocampal microstructural alterations and regional brain metabolism in early Alzheimer's disease: A combined DTI-PET study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2010.05.326 ◽

2010 ◽

Vol 6 ◽

pp. S104-S105

Author(s):

Andreas Fellgiebel ◽

Matthias Schreckenberger ◽

Matthias J. Müller ◽

Ingrid Schermuly ◽

Peter Stoeter ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Metabolism ◽

Microstructural Alterations ◽

Regional Brain ◽

Early Alzheimer’S Disease

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Alzheimer’s Disease-Related Neuropathology Among Patients with Medication Treated Type 2 Diabetes in a Community-Based Autopsy Cohort

Journal of Alzheimer s Disease ◽

10.3233/jad-210059 ◽

2021 ◽

pp. 1-10

Author(s):

Douglas Barthold ◽

Laura E. Gibbons ◽

Zachary A. Marcum ◽

Shelly L. Gray ◽

C. Dirk Keene ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Education ◽

Descriptive Analysis ◽

Neurofibrillary Tangle ◽

Apoe Genotype ◽

Severity Index ◽

Neuritic Plaque ◽

Braak Stage ◽

Total N

Background: Diabetes is a risk factor for Alzheimer’s disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC). Objective: This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications. Methods: Descriptive analysis of ADNC for Adult Changes in Thought (ACT) Study autopsy cohort who used diabetes medications, including sulfonylureas, insulin, and biguanides; total N = 118. ADNC included amyloid plaque distribution (Thal phasing), neurofibrillary tangle (NFT) distribution (Braak stage), and cortical neuritic plaque density (CERAD score). We also examined quantitative measures of ADNC using the means of standardized Histelide measures of cortical PHF-tau and Aβ 1–42. Adjusted analyses control for age at death, sex, education, APOE genotype, and diabetes complication severity index. Results: Adjusted analyses showed no significant association between any drug class and traditional neuropathologic measures compared to nonusers of that class. In adjusted Histelide analyses, any insulin use was associated with lower mean levels of Aβ 1–42 (–0.57 (CI: –1.12, –0.02)) compared to nonusers. Five years of sulfonylureas and of biguanides use was associated with lower levels of Aβ 1–42 compared to nonusers (–0.15 (CI: –0.28, –0.02), –0.31 (CI: –0.54, –0.07), respectively). Conclusion: Some evidence exists that diabetes medications are associated with lower levels of Aβ 1–42, but not traditional measures of neuropathology. Future studies are needed in larger samples to build understanding of the mechanisms between diabetes, its medications, and ADRD, and to potentially repurpose existing medications for prevention or delay of ADRD.

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

Current Alzheimer Research ◽

10.2174/1567205015666180601090533 ◽

2018 ◽

Vol 15 (10) ◽

pp. 938-950 ◽

Cited By ~ 4

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.

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