Importance of GWAS in finding un-targeted genetic association of sporadic Alzheimer’s disease

Bagaria, Jaya; Nho, Kwangsik; An, Seong Soo A.

doi:10.1007/s13273-021-00130-z

Cited by 6 publications

(3 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with dementia often display metabolic dysfunction with altered liver proteins. However, little is known about their cumulative effect on cognition (10). Our patient showed fewer signs of memory abilities despite exceedingly high levels of amyloid plaques, and low levels of tau build-up, similar to Christchurch homozygote mutation (67), however, it is interesting to note that similar to Christchurch heterozygous mutation, our patient too exhibited signs of spatial disorientation and progressive cognitive decline with an early onset of the disease (68).…”

Section: Discussionmentioning

confidence: 55%

“…Four major genetic loci have been related to AD, APOE (Apolipoprotein E) on chromosome 19, APP (Amyloid precursor protein) on chromosome 21 (3), PSEN1 (Presenilin-1), and PSEN2 (presenilin-2) on chromosome 14 and 1, respectively (4)(5)(6)(7)(8). Among these mutations, APP, PSEN1, and PSEN2 mutations represent only a minority of all patient's early-onset AD (EOAD) cases with a familial inheritance, suggesting that APOE (apolipoprotein E) on chromosome 19, may play an important role in disease onset in sporadic cases of EOAD (9,10). EOAD has a clinical manifestation before 65 years of age.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

Apolipoprotein (APOE) is implicated and verified as the main risk factor for early-onset Alzheimer's disease (AD). APOE is a protein that binds to lipids and is involved in cholesterol stability. Our paper reports a case of a sporadic early-onset AD (sEOAD) patient of a 54-year-old Korean man, where a novel APOE Leu159Pro heterozygous mutation was revealed upon Whole Exome Sequence analysis. The proband's CSF showed downregulated levels of Aβ42, with unchanged Tau levels. The mutation is in the Low-Density Lipoprotein Receptor (LDLR) region of the APOE gene, which mediates the clearance of APOE lipoproteins. LDLR works as a high-affinity point for APOE. Studies suggest that APOE-LDLR interplay could have varying effects. The LDLR receptor pathway has been previously suggested as a therapeutic target to treat tauopathy. However, the APOE-LDLR interaction has also shown a significant correlation with memory retention. Leu159Pro could be an interesting mutation that could be responsible for a less damaging pattern of AD by suppressing tau-association neurodegeneration while affecting the patient's memory retention and cognitive performance.

show abstract

Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Researchers have identified genetic mutations and non-genetic factors as causes of familial AD and sporadic AD (SAD), respectively. Non-genetic SAD account for 90% of all AD cases [84]. In addition, non-genetic factors play a greater role than genetic factors in the impairment of Aβ clearance [79].…”

Section: Other Mechanisms Of Aβ Clearancementioning

confidence: 99%

Alleviating the unwanted effects of oxidative stress on Aβ clearance: a review of related concepts and strategies for the development of computational modelling

Somin

Kulasiri

Samarasinghe

2023

Transl Neurodegener

View full text Add to dashboard Cite

Treatment for Alzheimer’s disease (AD) can be more effective in the early stages. Although we do not completely understand the aetiology of the early stages of AD, potential pathological factors (amyloid beta [Aβ] and tau) and other co-factors have been identified as causes of AD, which may indicate some of the mechanism at work in the early stages of AD. Today, one of the primary techniques used to help delay or prevent AD in the early stages involves alleviating the unwanted effects of oxidative stress on Aβ clearance. 4-Hydroxynonenal (HNE), a product of lipid peroxidation caused by oxidative stress, plays a key role in the adduction of the degrading proteases. This HNE employs a mechanism which decreases catalytic activity. This process ultimately impairs Aβ clearance. The degradation of HNE-modified proteins helps to alleviate the unwanted effects of oxidative stress. Having a clear understanding of the mechanisms associated with the degradation of the HNE-modified proteins is essential for the development of strategies and for alleviating the unwanted effects of oxidative stress. The strategies which could be employed to decrease the effects of oxidative stress include enhancing antioxidant activity, as well as the use of nanozymes and/or specific inhibitors. One area which shows promise in reducing oxidative stress is protein design. However, more research is needed to improve the effectiveness and accuracy of this technique. This paper discusses the interplay of potential pathological factors and AD. In particular, it focuses on the effect of oxidative stress on the expression of the Aβ-degrading proteases through adduction of the degrading proteases caused by HNE. The paper also elucidates other strategies that can be used to alleviate the unwanted effects of oxidative stress on Aβ clearance. To improve the effectiveness and accuracy of protein design, we explain the application of quantum mechanical/molecular mechanical approach.

show abstract

Transcriptomics Meta-Analysis Reveals Phagosome and Innate Immune System Dysfunction as Potential Mechanisms in the Cortex of Alzheimer’s Disease Mouse Strains

Widjaya,

Liu,

Lee

et al. 2023

J Mol Neurosci

View full text Add to dashboard Cite

Importance of GWAS in finding un-targeted genetic association of sporadic Alzheimer’s disease

Cited by 6 publications

References 106 publications

Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease

Whole Exome Sequencing Reveals a Novel APOE Mutation in a Patient With Sporadic Early-Onset Alzheimer's Disease

Alleviating the unwanted effects of oxidative stress on Aβ clearance: a review of related concepts and strategies for the development of computational modelling

Transcriptomics Meta-Analysis Reveals Phagosome and Innate Immune System Dysfunction as Potential Mechanisms in the Cortex of Alzheimer’s Disease Mouse Strains

Contact Info

Product

Resources

About