Peripheral Transport Proteins Were Associated with 4-Year Cognitive Decline in APOE ɛ4 Non-Carriers: A Longitudinal, Population-Based Study.

Abstract

BACKGROUND:

Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid-β (Aβ).

OBJECTIVE:

To determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE) on their association.

METHODS:

Cognitively normal subjects were followed-up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini-Mental State Examination (MMSE), and cognitive decline was defined as a ≥2-point decrease of MMSE after 4 years. The association between baseline sLRP1/sRAGE and 4-year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship.

RESULTS:

769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4-year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13-3.86, p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE ɛ4 non-carriers (adjusted OR = 1.60, 95% CI: 1.04-2.48, p = 0.034).

CONCLUSION:

Individuals with lower levels of sRAGE had an increased risk of 4-year cognitive decline in APOE ɛ4 non-carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.

• Authors: Ling Gao, Liangjun Dang, Shan Wei, Ningwei Hu, Fan Gao, Wei Peng, Suhang Shang, Yi Zhao, Chen Chen, Xiaojuan Guo, Kang Huo, Jingyi Wang, Jin Wang, Qiumin Qu
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 86 Issue 2 Pg. 801-812 ( 2022) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 35124644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Apolipoprotein E4
• Apolipoproteins E
• Carrier Proteins
• Receptor for Advanced Glycation End Products
• sRAGE protein, human

Topics

• Amyloid beta-Peptides (metabolism)
• Apolipoprotein E4 (genetics, metabolism)
• Apolipoproteins E (genetics)
• Carrier Proteins (genetics)
• Cognitive Dysfunction (diagnosis, genetics)
• Genotype
• Humans
• Longitudinal Studies
• Receptor for Advanced Glycation End Products (blood)