Interaction effects between variants in TOMM40 and PVRL2 with plasma amyloid-β and Alzheimer's disease among Chinese older adults: a population-based study

Abstract Background Emerging evidence has linked TOMM40 and PVRL2 polymorphisms with Alzheimer’s disease (AD). We examined their associations with AD and plasma AD biomarkers and interaction on AD risk among Chinese older adults. Methods This population-based study included 4876 participants (age ≥ 65 years, 57.2% women) from MIND-China. TOMM40(rs2075650) and PVRL2(rs6859) polymorphisms were detected using multiple-polymerase chain reaction amplification. Plasma Aβ40, Aβ42, and t-tau were measured using SIMOA in a subsample (n = 1257). Data was analyzed using multiple logistic and general linear regression models. Results AD was diagnosed in 182 participants. The multi-adjusted odds ratio of AD was 6.24(95%CI 1.73–22.48) for TOMM40GG (vs. AA), 1.47(0.89–2.42) for PVRL2AA (vs. GG), and 12.87(3.97–41.73) for having both risk alleles (Pinteraction=0.0003). In the plasma biomarker subsample, TOMM40GG was significantly associated with lower plasma Aβ42 and the Aβ42-to-Aβ40 ratio (p < 0.05). Conclusions TOMM40 and PVRL2 genes could interact to substantially increase the likelihood of AD, possibly through influencing Aβ metabolism.

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Association and interaction of TOMM40 and PVRL2 with plasma amyloid-β and Alzheimer's disease among Chinese older adults: a population-based study

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2021.12.013 ◽

2022 ◽

Author(s):

Xiaoyan Liang ◽

Cuicui Liu ◽

Keke Liu ◽

Lin Cong ◽

Yongxiang Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Population Based ◽

Population Based Study ◽

Chinese Older Adults

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Association and Interaction of TOMM40 and PVRL2 with Plasma Amyloid-Β and Alzheimer's Disease Among Chinese Older Adults: A Population-Based Study

SSRN Electronic Journal ◽

10.2139/ssrn.3914659 ◽

2021 ◽

Author(s):

Xiaoyan Liang ◽

Cuicui Liu ◽

Keke Liu ◽

Lin Cong ◽

Yongxiang Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Population Based ◽

Population Based Study ◽

Chinese Older Adults

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Dissociated amyloid-β antibody levels as a serum biomarker for the progression of Alzheimer’s disease: A population-based study

Experimental Gerontology ◽

10.1016/j.exger.2009.10.003 ◽

2010 ◽

Vol 45 (1) ◽

pp. 47-52 ◽

Cited By ~ 21

Author(s):

Katarzyna A. Gustaw-Rothenberg ◽

Sandra L. Siedlak ◽

David J. Bonda ◽

Alan Lerner ◽

Massimo Tabaton ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Population Based ◽

Serum Biomarker ◽

Population Based Study ◽

Antibody Levels

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Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-200759 ◽

2021 ◽

pp. 1-13

Author(s):

Jonathan D. Drake ◽

Alison B. Chambers ◽

Brian R. Ott ◽

Lori A. Daiello ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Functional Impairment ◽

Amyloid Β ◽

Intercellular Adhesion Molecule ◽

Csf Biomarkers ◽

Linear Regression Models ◽

Cognitively Normal

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer’s disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. Objective: We utilized Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). Results: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ 42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ 42 (all < p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. Conclusion: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.

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P2-126: Clinical, cognitive, neuropsychiatric and genetic predictors of conversion from amnestic mild cognitive impairment to Alzheimer's disease in Chinese older adults

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.1014 ◽

2011 ◽

Vol 7 ◽

pp. S349-S349

Author(s):

Leung-wing Chu

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amnestic Mild Cognitive Impairment ◽

Chinese Older Adults ◽

Genetic Predictors

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Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

Journal of Alzheimer s Disease ◽

10.3233/jad-210333 ◽

2021 ◽

pp. 1-11

Author(s):

Fennie Choy Chin Wong ◽

Seyed Ehsan Saffari ◽

Chathuri Yatawara ◽

Kok Pin Ng ◽

Nagaendran Kandiah ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Amyloid Β ◽

Intracranial Volume ◽

Linear Regression Models ◽

Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

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