Early diagnosis of Alzheimer’s disease: Is it doable?

by Onkgopotse Ntloana

Alzheimer’s Disease (AD) is a chronic, progressive, and neurological disease characterized by persistent declines in memory, thinking, language, and learning capacity, eventually leading to full-blown dementia, complete reliance on others for basic daily activities, and untimely death. It is an incurable condition that affects over 24 million individuals globally and accounts for 60–80% of all dementia cases world-wide. Damage to a person’s brain caused by AD manifests itself in early clinical indications and symptoms. Symptoms occur around the mid-60s for most patients with AD, especially those who have the late-onset form. Early-onset AD manifests itself between the ages of 30 and 60.

The risk of developing AD increases with age; it is a neurological disease that is not publicly spoken off – which leads to the lack of understanding of the disease, prevention, and how to take care of a person who has AD. The authors of a recently released paper, Systems biology and bioinformatics approach to identify gene signatures, pathways and therapeutic targets of Alzheimers disease, set out to discover biomarker signatures in the blood that could help the diagnosis of AD at an early stage and so add valuable information to our understanding of the molecular mechanisms that underlie AD.

With this goal in mind, they investigated biomarkers that are expressed under comparable genetic control in both cells using eQTL data to uncover biomarkers that are expressed under similar genetic control in both cells (using microarray data). They investigated human genomic and transcriptome data and examined the involvement of genes on pathogenic processes using curated gold benchmark databases for AD to discover prospective biomarkers and biochemical pathways of the brain that behave similarly in blood.

The authors identified 29 significant drug targets and candidate drugs. They discovered significant genes that are correlated with the progression of AD including neurodevelopmental disorder genes that are associated with AD. The growth-associated protein 43 (GAP-43) has been linked to both the diagnostic and neuropathology of AD, and hence could be used as a biomarker for the disease. The GAP-43 gene produces considerable molecular damage that occurs before and throughout AD. Hepatocyte growth factor (HGF) is found in increased concentrations in neurons, other nervous system tissues, and cerebrospinal fluid in AD patients. Wnt signaling is enhanced, GSK3 function is reduced, and Tau phosphorylation is reduced as the expression of WNT inhibitory factor-1 (WIF1) decreases from healthy people to AD patients.

Because TFs and miRNAs have a big impact on gene expression at the transcriptional and post-transcriptional levels, they could be used as biomarkers. The RAR related orphan receptor B (RORB) has recently been identified as the cause of the specific susceptibility of entorhinal cortex neurons that defines AD. HNF1 homeobox B (HNF1B) is linked to type 2 diabetes, particularly in the elderly. SNPs in myeloid zinc finger 1 (MZF1), which regulates inflammatory response and cholesterol metabolism, have been linked to AD.

The lack of a laboratory-based blood test for AD limits diagnosis based on a physician’s physical examination and clinical history. Biomarkers are required to diagnose, monitor, and treat any disease, thus identifying prospective biomarkers from tissues that are easily accessible in the clinic, such as blood cells, is critical. The discovered biomarkers and molecular pathways may provide fresh insight into AD progression, early diagnosis, and therapeutic advancements.

References

Chowdhury, U.N., Islam, M.B., Ahmad, S., Moni, M.A. 2020. Systems biology and bioinformatics approach to identify gene signatures, pathways and therapeutic targets of Alzheimer’s disease. Informatics in Medicine Unlocked, 21(1), e100439. https://doi.org/10.1016/j.imu.2020.100439  

John Hopkins Medicine. 2021. Early-onset Alzheimer’s Disease. https://www.hopkinsmedicine.org/health/conditions-and-diseases/alzheimers-disease/earlyonset-alzheimer-disease Date of access: 29 Jul. 2021.  

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