Panel of Genetic Variations as a Potential Non-invasive Biomarker for Early Diagnosis of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia. Biomarkers such as levels of amyloid beta (Aβ) in cerebrospinal fluid and ApoE genotyping were suggested for the diagnosis of AD, however, the result is either non-conclusive or with invasive procedure. Genome-wide association studies (GWASs) for AD suggested single nucleotide polymorphisms (SNPs) in many genes are associated with the risk of AD, but each only contributed with small effect to the disease. By incorporating a panel of established genetic susceptibility factors, the risk of an individual in getting AD could be better estimated. Further research will be required to reveal if adding to the current well-developed clinical diagnosis protocol, the accuracy and specificity of diagnosis of AD would be greatly improved and if this might also be beneficial in identifying pre-symptomatic AD patients for early diagnosis and intervention of the disease.

The Serum Levels of Resistin and Its Relationship with Other Proinflammatory Cytokines in Patients with Alzheimer’s Disease

“…Although there have been several hypotheses available for the etiopathology of AD, it is well-known that there is a chronic inflammatory process in the brain of AD. 21 , 22) Activated microglia and astrocytes excessively secrete inflammatory components including pro-inflammatory cytokines, reactive oxygen species, chemokines, macrophage inflammatory proteins, and complements. 7) Those inflammatory molecules secreted, certain cytokines in particular, disturb the balance of normal neurophysiologic condition, which is related to cognition, learning, and memory.…”

Cognitive variability—A marker for incident MCI and AD: An analysis for the Alzheimer's Disease Neuroimaging Initiative

“…These predictors can only be obtained with a lumbar puncture (LP) or neuroimaging of cerebral amyloid plaques, requiring injection of a radioactive compound, and access to unique scanning expertise [30]. At minimum, other biomarkers entail specialized neuroimaging and often require longitudinal follow‐up [8,9]. For example, MRI measurement of HVL is highly accurate in predicting conversion from MCI to AD [31,32]; however, volume loss can only be measured with repeated evaluations.…”

“…The most promising biomarkers are obtained from cerebrospinal fluid and brain imaging [7]. However, given the difficulties in disseminating collection methods outside of research centers, and the arduous and invasive nature of some collection procedures, there is a desire to develop noninvasive, convenient markers [8,9]. The development of a cognitive marker, once established and validated, would offer an alternative for individuals unable or unwilling to submit to the collection of traditional biomarkers.…”

Genetics and epigenetics of Alzheimer's disease

“…The AlzGene database provides a comprehensive, unbiased and regularly updated field synopsis of genetic association studies performed in AD 21. According to the AlzGene database, the top 10 genes showing the strongest association with AD are APOE, BIN1, CLU, ABCA7 (ATP-binding cassette transporter), CR1, PICALM, membrane spanning 4-domains subfamily (MS4A6A), CD33, MS4A4E and CD2-associated protein (CD2AP) 22. As previously stated, the gene encoding APOE, which was discovered more than 15 years ago, contributes the largest disease risk.…”

“…CD2AP regulates the actin cytoskeleton and is involved in the regulation of receptor mediated endocytosis. Bridging integrator 1 and ABCA7 are also replicated LOAD genes, involved in the four pathways (amyloid protein synthesis, immune system function, lipid metabolism and membrane synaptic transmission) leading to AD22 39 (see table 1). The genes in the MS4A cluster are located on chromosome 11 and encode proteins with at least four potential transmembrane domains, but their specific functions have not yet been well characterised.…”