Genetic variants of BIN1, APOE gene and GDF15 protein concentration in Alzheimer's disease patients

TL;DR

This study explores how genetic variants of BIN1 and APOE, along with GDF15 protein levels, relate to Alzheimer's disease and dementia risk.

Contribution

The study reveals novel associations between BIN1 genotype, APOE alleles, and GDF15 levels in Alzheimer's patients and controls.

Findings

Higher GDF15 levels were found in CU compared to CR and similar in CR and AD.

BIN1 TT genotype showed the highest GDF15 levels in both CR and AD.

APOE ε3ε3 individuals had 2-3 times higher GDF15 levels in CR and AD.

Abstract

Currently, Alzheimer's disease (AD) risk genetic variants include among others APOE and BIN1. APOE possesses 3 alleles: protective (ε2), neutral (ε3), and pathogenic (ε4). APOE gene is present in amyloid plaques and binds to Aβ peptides. BIN1 gene is involved in the regulation of apoptosis and immune response. Growth and differentiation factor 15 (GDF15) is an inflammation‐associated hormone and, with diseases with inflammatory etiologies. GDF15 was shown to be associated with incident dementia including AD. Moreover, GDF15 is thought to be important in predicting dementia in both the long and short term. Individuals with higher levels of GDF15 are more likely to develop dementia. The role of GDF15 is poorly defined

The aim of the study was to analyze the APOE and BIN1 genetic variants and GDF15 protein concentration in AD patients and related (CR), and unrelated (CU) controls with AD. The studies were conducted on 29 patients with AD. The control group included 25 CR and 27 CU. The APOE genotype was determined by real‐time PCR. The BIN1 genotypes were determined by HRM and sequencing. GDF15 levels were analyzed by the ELISA method.

The study showed statistically significantly higher levels of GDF15 in CU compared to CR (p = 0.048) and similar levels in CR and AD. In CU carriers of APOE ε3ε3 and ε3ε4 (p = 0.0946) alleles trend towards higher GDF15 levels were demonstrated as compared with CR and AD. At the same time, CU with the BIN1 CC genotype showed statistically significantly lower GDF15 levels compared to AD with BIN1 CC (p = 0.050). The highest GDF15 levels were shown in individuals with the BIN1 TT genotype, both CR and AD. In contrast to CU in CR and AD, only in APOE ε3ε3 individuals, the GDF15 protein level was 2‐3 times higher than the average score in the analyzed group.

GDF15 appears to be more strongly involved in the development of dementia with immune regulatory factors (BIN1 TT genotype).