Dataset Information

Effect of APOE Genotype on Synaptic Proteins in Earlier Adult Life.

ABSTRACT:

Background

Possession of APOEɛ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease.

Objective

We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins.

Methods

We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior temporal gyrus from 103 adults aged <75 without dementia. Corresponding gene expression was measured by RT-PCR.

Results

There was no evidence that ɛ4 affected levels of the proteins measured. Instead we found an increase in post-synaptic proteins in the hippocampi of those with an ɛ32 genotype. The evidence was strongest for drebrin (p = 0.011). There was some evidence of increased synaptic protein gene expression in ɛ4 carriers.

Conclusions

People with an APOEɛ32 genotype have a reduced risk of Alzheimer's disease. It may be relevant that they have a higher level of post-synaptic proteins in the hippocampus even in earlier adulthood.

SUBMITTER: Sinclair LI

PROVIDER: S-EPMC5545905 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Effect of APOE Genotype on Synaptic Proteins in Earlier Adult Life.

Sinclair Lindsey I LI Love Seth S

Journal of Alzheimer's disease : JAD 20170101 3

<h4>Background</h4>Possession of APOEɛ4 is a strong risk factor for late-onset Alzheimer's disease and is associated with loss of synaptic proteins in the elderly even in the absence of Alzheimer's disease.<h4>Objective</h4>We hypothesized that ɛ4 allele possession in non-demented adults aged under-75 would also be associated with alterations in the levels of synaptic proteins.<h4>Methods</h4>We measured synaptophysin, PSD95, drebrin, SNAP-25, and septin 7 by ELISA in hippocampus and superior te ...[more]

PMID: 28731446

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Project description:The enzyme methylenetetrahydrofolate reductase (MTHFR) is a part of the homocysteine and folate metabolic pathways, affecting the methylations of DNA, RNA, and proteins. Mthfr deficiency was reported as a risk factor for neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. Neonatal disruption of the GABAergic system is also associated with behavioral outcomes. The interaction between the epigenetic influence of Mthfr deficiency and neonatal exposure to the GABA potentiating drug vigabatrin (GVG) in mice has been shown to have gender-dependent effects on mice anxiety and to have memory impairment effects in a gender-independent manner. Here we show that Mthfr deficiency interacts with neonatal GABA potentiation to alter social behavior in female, but not male, mice. This impairment was associated with a gender-dependent enhancement of proteins implicated in excitatory synapse plasticity in the female cortex. Reelin and fragile X mental retardation 1 protein (FMRP) levels and membrane GluR1/GluR2 ratios were elevated in wild-type mice treated neonatally with GVG and in Mthfr+/- mice treated with saline, but not in Mthfr+/- mice treated with GVG, compared with control groups (wild type treated with saline). A minor influence on the levels of these proteins was observed in male mice cortices, possibly due to high basal protein levels. Interaction between gender, genotype, and treatment was also observed in the GABA pathway. In female mice, GABA A?2/gephyrin ratios were suppressed in all test groups; in male mice, a genotype-specific enhancement of GABA A?2/gephyrin was observed. The lack of an effect on either reln or Fmr1 transcription suggests post-transcriptional regulation of these genes. Taken together, these findings suggest that Mthfr deficiency may interact with neonatal GABA potentiation in a gender-dependent manner to interrupt synaptic function. This may illustrate a possible mechanism for the epigenetic involvement of Mthfr deficiency in neurodevelopmental disorders.

Dataset Information

Effect of APOE Genotype on Synaptic Proteins in Earlier Adult Life.

Background

Objective

Methods

Results

Conclusions

Publications

Effect of APOE Genotype on Synaptic Proteins in Earlier Adult Life.

Similar Datasets

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