The Relationship between Alzheimer’s Disease, Inflammation, the APOE Genotype and Neuronal Integrity

ABSTRACT

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with progressive

neuronal loss. Microglial cell activation in the central nervous system (CNS) may

contribute to this process through the release of neurotoxic inflammatory mediators.

Systemic inflammation, through signaling to the CNS, can further activate microglia and

thus accelerate neurodegeneration. The apolipoprotein (APOE) ε4 allele has been

associated with both an increased risk of developing AD and higher levels of

inflammation. The aim of this study was to investigate the relationships between systemic

inflammation, CNS inflammation, the APOE genotype, neuronal integrity and cognitive

functioning in a cohort of elderly participants from the Western Cape region of South

Africa. South Africa is a developing country where systemic infections are common and

the ε4 allelic frequency is thought to be high. Sixty-eight cognitively healthy controls and

60 AD participants were recruited. Participants underwent a full clinical and cognitive

assessment. APOE genotyping was performed and the following systemic inflammatory

markers were measured: erythrocyte sedimentation rate (ESR), white cell count, monocyte

count, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), transforming

growth factor- beta (TGF-β), IL-10 and osteopontin. Forty-eight control and 32 AD

participants were re-assessed after one-year. Thirty-three participants underwent proton

magnetic resonance spectroscopy for the detection of myo-inositol (MI), a marker of glial

activation, and N-acetylaspartate and N- acetylaspartylglutamate (NAA+NAAG), a

neuronal integrity marker, in the posterior cingulate gyrus. Results showed that mild AD

participants had higher ESRs and IL-1β levels when compared with moderate AD, more

severe AD and control participants. High baseline levels of TNF-α, low baseline levels of

IL-10 and the presence of the ε4 allele were independently associated with a greater

cognitive decline in AD. MI was increased in more severe AD participants and tended to

be negatively correlated with episodic memory performance. NAA+NAAG levels were

lower in AD participants compared with controls. In conclusion, the inflammatory

response in AD changed with disease progression. Pro-inflammatory systemic changes

were seen early in the disease but glial activation in the CNS was observed later. Thus,

systemic inflammation may drive CNS inflammation and neurodegeneration. The ε4 allele

had a detrimental effect in AD. The mechanism by which ε4 exerts its detrimental effects

may relate to suppression of a protective anti-inflammatory response.

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APA

GRACE, L (2021). The Relationship between Alzheimer’s Disease, Inflammation, the APOE Genotype and Neuronal Integrity. Afribary. Retrieved from https://afribary.com/works/the-relationship-between-alzheimer-s-disease-inflammation-the-apoe-genotype-and-neuronal-integrity

MLA 8th

GRACE, LAURIAN "The Relationship between Alzheimer’s Disease, Inflammation, the APOE Genotype and Neuronal Integrity" Afribary. Afribary, 25 Apr. 2021, https://afribary.com/works/the-relationship-between-alzheimer-s-disease-inflammation-the-apoe-genotype-and-neuronal-integrity. Accessed 22 Jul. 2024.

MLA7

GRACE, LAURIAN . "The Relationship between Alzheimer’s Disease, Inflammation, the APOE Genotype and Neuronal Integrity". Afribary, Afribary, 25 Apr. 2021. Web. 22 Jul. 2024. < https://afribary.com/works/the-relationship-between-alzheimer-s-disease-inflammation-the-apoe-genotype-and-neuronal-integrity >.

Chicago

GRACE, LAURIAN . "The Relationship between Alzheimer’s Disease, Inflammation, the APOE Genotype and Neuronal Integrity" Afribary (2021). Accessed July 22, 2024. https://afribary.com/works/the-relationship-between-alzheimer-s-disease-inflammation-the-apoe-genotype-and-neuronal-integrity