Double blow to the brain
APOE gene is associated with tau protein aggregation in Alzheimer's disease
Angelina Stolyarova, PCR.news
The association of β-amyloid deposits in the brain with the allele e4 of the apolipoprotein gene (APOE) in Alzheimer's disease (AD) has been proven, however, there is a link between cerebral β-amyloidosis (Aß) and the allele of apolipoprotein E (AOE) e4, however, the involvement of APOE e4 in tau pathology has so far been unclear. Scientists from the USA conducted a study on 350 volunteers to close this gap.
Using PET and MRI, they studied the distribution of beta-amyloid and tau protein aggregates in the participants' brains, and also measured the volumes of individual regions. In addition, the scientists determined the hyperphosphorylated tau protein in the cerebrospinal fluid and the genotypes of the patients' AOE.
The APOE gene has three alleles: e3, e4 and e2. The allele e2 is associated with a reduced risk of AD compared to e3, whereas e4 increases the risk of dementia in AD and is associated with an earlier onset of the disease. In a new study, carriers of APOE e4 had more amyloid plaques in the brain compared to non-carriers. Plaques were often found in the cerebral cortex, amygdala, hippocampus and basal nucleus. APOE e4 carriers were also characterized by high levels of tau protein in the temporal region, hippocampus and amygdala. Based on the data obtained, the scientists built a model with which they established that the interaction of e4 and beta-amyloid leads to an increase in the amount of tau protein. For patients who are not carriers of this allele, but with amyloid plaques, no such association was observed. In this case, APOE e4 affected only insoluble, aggregated forms of tau protein. No associations with APOE e4 and amyloid pathology were found for phosphorylated tau protein in cerebrospinal fluid.
"Carriers of APOE e4 are more likely to start accumulating amyloid, which puts them on the path to Alzheimer's disease," explains the main author of the work, Brian Gordon, associate professor of radiology at the Mallinkrodt Institute of Radiology at Washington University School of Medicine in St. Louis. — Then, with the same amount of amyloid, they get more tau tangles, which leads to increased atrophy. It's a double blow to the brain."
Further analysis revealed a greater effect of APOE e4 on β-amyloid deposits in women compared to men. This confirms previous research by scientists on the relationship between gender and the development of AB.
Finally, the scientists compared the data on the expression of the APOE gene in different brain regions collected in the AHBA atlas with the localization of amyloid and tau pathology. They found that in carriers of APOE e4, the regions with the highest level of gene expression corresponded to the localization sites of tau protein aggregates. This means that the expression of AROE can determine the vulnerability of various areas of the brain to taupathy.
In the future, the authors plan to study the relationship between gene expression patterns and tau protein aggregation in patients with atypical manifestations of AD, for example, with impaired vision and speech before the onset of dementia.
Article by Dincer et al. APOE e4 genotype, amyloid-β, and sex interact to predict tau in regions of high APOE mRNA expression is published in the journal Science Translational Medicine.
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