Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly

Choi, Hyo Jung; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Baek, Hye W.; Lee, Jun Ho; Kim, Hyun Jung; Han, Ji Young; Yoon, Eun Jin; Kim, Yu Kyeong; Woo, Jong Inn; Lee, Dong Hoon

doi:10.1016/j.jagp.2016.03.001

Cited by 18 publications

(20 citation statements)

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“…For example, mouse studies showed that serum TG levels were elevated prior to amyloid deposition, 25 while human studies showed increased serum TGs were associated with increased amyloidosis in cognitively normal individuals. 3 Longitudinal studies showed that increased midlife TGs predicted amyloidosis and tau pathology 20 years later, 2 providing additional evidence for the early influence of TGs in AD. Thus, it is particularly interesting that we found a selective association of PUTGs with CSF Aβ only in APOE ε4 carriers.…”

Section: Discussionmentioning

confidence: 99%

“…No relationship between AD and total TGs has been reported, 1 while others suggest that elevated TGs early in life represented a risk factor for increased amyloidosis 20 years later. 2,3 Finally, others found that individuals with probable AD had significantly decreased serum TG levels. 4,5 Apolipoprotein E (APOE) ε4 carrier status may serve as a risk factor for altered TG levels in AD.…”

Section: Introduction: 240/250mentioning

confidence: 98%

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Serum triglycerides in Alzheimer’s disease: Relation to neuroimaging and CSF biomarkers

Bernath

Bhattacharyya

Nho

et al. 2018

Preprint

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word count: 235/250 words Text word count: 3703/4500 words Abstract (235/250 words) Objective: To investigate the association of triglyceride (TG) principal component scores with Alzheimer's disease (AD) and the "A/T/N/V" (Amyloid, Tau, Neurodegeneration, and Cerebrovascular disease) biomarkers for AD. Methods: Serum levels of 84 TG species were measured using untargeted lipid profiling of 689 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort including 190 cognitively normal older adults (CN) and 339 mild cognitive impairment (MCI) and 160 AD. Principal component analysis with factor rotation was used for dimension reduction of TG species. Differences in principal components between diagnostic groups and associations between principal components and AD biomarkers (including CSF, MRI and [18F]FDG-PET)were assessed using a multivariate generalized linear model (GLM) approach. In both cases, the Bonferroni method of adjustment was employed to correct for multiple comparisons. Results:The 84 TGs yielded 9 principal components, two of which consisting of long-chain, polyunsaturated fatty acid-containing TGs (PUTGs), were significantly associated with MCI and AD. Lower levels of PUTGs were observed in MCI and AD compared to CN. PUTG principal component scores were also significantly associated with hippocampal volume and entorhinal cortical thickness. In participants carrying APOE ε4 allele, these principal components were significantly associated with CSF amyloid-β1-42 values and entorhinal cortical thickness. Conclusions:This study shows PUTG component scores significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in APOE ε4 carriers. Replication in independent larger studies and longitudinal follow-up are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introduction: 240/250mentioning

confidence: 98%

Serum triglycerides in Alzheimer’s disease: Relation to neuroimaging and CSF biomarkers

Bernath

Bhattacharyya

Nho

et al. 2018

Preprint

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“…Previous studies of weight loss in older adults have shown similar results . Triglycerides are an emerging treatment target as their level is proportional to risk of cardiovascular disease, and triglyceride levels correlate with cerebral amyloid burden . However, it is currently unclear whether triglyceride lowering with medications (or indeed diet) reduce the risk of cardiovascular disease in the long term …”

Section: Discussionmentioning

confidence: 83%

“…7 Triglycerides are an emerging treatment target as their level is proportional to risk of cardiovascular disease, 25 and triglyceride levels correlate with cerebral amyloid burden. 26 However, it is currently unclear whether triglyceride lowering with medications (or indeed diet) reduce the risk of cardiovascular disease in the long term. 25,27 Low-grade, systemic inflammation (meta-inflammation) is central to the pathophysiology of cardiovascular disease 28 and degenerative diseases of ageing.…”

Section: Discussionmentioning

confidence: 99%

Obesity in older adults: Effect of degree of weight loss on cardiovascular markers and medications

et al. 2019

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Summary Obesity worsens the age‐related tendency towards cardiovascular disease and diabetes. Older adults are vulnerable to medication adverse effects. Intentional weight loss in older adults with obesity has been shown to improve cardiovascular and glycaemic markers. The effect of rapid weight loss induced by very‐low‐calorie diets (VLCDs) on these markers has not been evaluated in this group. In this 12‐week study, participants were randomized to one of healthy eating, hypocaloric diet or VLCD, all combined with three times weekly exercise (Ex/HE, Ex/Diet, Ex/VLCD, respectively). The effects of these interventions on weight, blood pressure, lipids, glucose and HbA1c, inflammatory markers and cardiovascular and diabetes medication changes were measured. Weight loss was 3.7%, 5.1% and 11.1% in Ex/HE, Ex/Diet and Ex/VLCD, respectively. There were significant improvements in HbA1c in all groups, but by the greatest degree in Ex/VLCD (0.18 ± 0.07%, 0.18 ± 0.06% and 0.59 ± 0.13%, respectively). Similar patterns were seen in total cholesterol (0.13 ± 0.15, 0.21 ± 0.11 and 0.53 ± 0.13 mmol/L, respectively, P = .047), triglycerides (0.35 ± 0.13, 0.20 ± 0.10 and 0.51 ± 0.09 mmol/L, respectively, P = .011) and systolic blood pressure (9 ± 2, 2 ± 3 and 14 ± 3 mmHg respectively, P = .025). There were no between‐group differences in fasting glucose, high‐density lipoprotein (HDL) cholesterol, LDL‐C and inflammatory markers. Reductions in anti‐hypertensive or diabetes medication were made in 4/29, 7/36 and 16/37 participants in Ex/HE, Ex/Diet and Ex/VLCD, respectively (P = .017). Significant weight loss achieved with a VLCD gave rise to improvements in multiple cardiovascular risk markers, despite reduction in medication. Weight loss is an under‐utilized method of cardiovascular risk management in this group.

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“…Mamo et al found that Aβ was associated with plasma lipoproteins, especially those enriched with TG, and that TG-rich lipoprotein particles in blood may serve as Aβ carriers [49]. The circulating TG-rich lipoprotein-Aβ complex may compromise blood-brain barrier (BBB) integrity and ultimately increased cerebral amyloid deposition [50]. Therefore, TG has both protective and promotive roles.…”

Section: Discussionmentioning

confidence: 99%

PVRL2 rs6859 Modifies the Effect of Triglyceride on Progression of Mild Cognitive Impairment: The Shanghai Aging Study

Wang

Ding

Atibaike

et al. 2020

Preprint

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Background Mild cognitive impairment (MCI) is an intermediate stage between normal cognition and Alzheimer’s disease (AD). Genome-wide association studies (GWAS) have identified many AD-risk variants and indicated the important role of lipid metabolism pathway in AD progression. This study aimed to investigate the effects of triglyceride (TG) and genetic risk factors on progression from MCI to AD (MCI-AD progression).Methods The current study sample comprised of 305 MCI subjects aged 50 and over who were prospectively followed up for average 4.5 years in a sub-cohort of the Shanghai Aging Study. A consensus diagnosis of incident AD was conducted according to Diagnostic and Statistical Manual of Mental Disorders-IV and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria. Fasting blood samples were obtained at baseline for analyzing serum TG. Single nucleotide polymorphisms (SNPs) genotyping was performed using a MassARRAY system. The effect of TG, genetic variants and their interaction on MCI-AD progression were analyzed using Cox proportional hazards regression model.Results During a mean (±SD) follow-up period of 4.5±1.3 y, 58 subjects developed incident AD. The SNP, rs6859 in the Poliovirus Receptor–Related 2 (PVRL2) gene, was significantly associated with incident AD (false discovery rate (FDR)-adjusted P = 0.018). In multivariate cox model, the PVRL2 rs6859 AG, AA and AG+AA genotypes were associated with significantly increased incident AD, compared with the GG genotype (hazard ratio [HR] = 2.29, P = 0.029, and HR = 2.92, P = 0.013, and HR = 2.47, P =0.012, respectively). In PVRL2 rs6859 AG/AA carriers, higher ln TG was significantly associated with increased risk of incident AD (adjusted HR =2.64, P = 0.034). Ln TG and PVRL2 rs6859 had interactive effect on the MCI-AD progression (P Ln TG × rs6859 = 0.001). Conclusion The present study indicated that PVRL2 rs6859 modified the effect of TG on MCI-AD progression. Precision prevention in MCI population based on genetic information should be considered to avoid progression to AD.

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Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly

Cited by 18 publications

References 36 publications

Serum triglycerides in Alzheimer’s disease: Relation to neuroimaging and CSF biomarkers

Serum triglycerides in Alzheimer’s disease: Relation to neuroimaging and CSF biomarkers

Obesity in older adults: Effect of degree of weight loss on cardiovascular markers and medications

PVRL2 rs6859 Modifies the Effect of Triglyceride on Progression of Mild Cognitive Impairment: The Shanghai Aging Study

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