A rare variant in the sortilin-related receptor 1 gene is associated with declined cognitive functions in the elderly

Stepanov, Vadim; Бочарова, А. В.; Вагайцева, К. В.; Marusin, Andrey; Markova, Valentina V.; Минайчева, Л. И.; Жукова, И. А.; Жукова, Н. Г.; Алифирова, В. М.; Makeeva, O. A.

doi:10.17116/jnevro20181185192

Cited by 2 publications

(2 citation statements)

References 22 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acting as a sorting receptor, SORL1 directs APP away from amyloidogenic processing pathways, thereby reducing the production of Aβ peptides. However, genetic variations in SORL1 can impair its function, leading to increased amyloidogenic processing of APP and elevated levels of the more amyloidogenic form of Aβ, Aβ42 [91,92]. Furthermore, SORL1 dysfunction is linked to increased tau phosphorylation and the formation of neuro brillary tangles (NFTs) in Alzheimer's disease.…”

Section: In Uence On Biochemical Pathways and Cellular Processesmentioning

confidence: 99%

“…Elevated Aβ levels resulting from impaired SORL1 function can trigger downstream events, leading to tau hyperphosphorylation and the aggregation of tau protein into NFTs. Additionally, SORL1 is involved in regulating lipid metabolism and cholesterol homeostasis, in uencing the tra cking of lipoproteins and lipid receptors within neurons, thus affecting lipid uptake and metabolism [91,92].…”

Section: In Uence On Biochemical Pathways and Cellular Processesmentioning

confidence: 99%

See 1 more Smart Citation

Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability

Shafi,

Siddiqui

2024

Preprint

View full text Add to dashboard Cite

Background: Alzheimer's disease (AD) is a neurodegenerative disorder influenced by genetic and environmental factors. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33 play key roles in AD pathogenesis, affecting biochemical pathways and cellular processes. However, the interaction between genetic predisposition and environmental factors, as well as the reasons for variability in disease phenotype, remain poorly understood. This study aims to investigate these interactions to improve our understanding of AD etiology and inform personalized interventions. Methods: A comprehensive search encompassing databases such as PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals was conducted to retrieve relevant articles for the investigation of genes involved in Alzheimer's disease (AD) pathogenesis, including APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33. Articles were searched without any date restrictions. Utilizing the criteria delineated in the methodology section, studies were systematically reviewed to elucidate how environmental factors and genetics influence Alzheimer's disease onset, progression, symptom severity, and progression rates. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: Our investigation revealed the complicated interactions between genetic predisposition, environmental factors, biochemical pathways, and cellular processes in Alzheimer's disease (AD) pathogenesis. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33 influence amyloid-beta production, tau pathology, lipid metabolism, and inflammation in AD. These genes interact with environmental factors such as diet, pollutants, head trauma, and lifestyle, modulating disease risk and progression. Additionally, we found variability in disease phenotype among individuals carrying similar genetic mutations, influenced by genetic modifiers, environmental factors, cognitive reserve, and neurobiological differences. Conclusion: Alzheimer's disease (AD) is a multifactorial disorder influenced by genetic and environmental factors. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, and CD33 play critical roles in AD pathogenesis by affecting amyloid-beta production, tau pathology, lipid metabolism, and inflammation. These genes interact with environmental factors such as diet, pollutants, head trauma, and lifestyle, further modulating disease risk and progression. Understanding these complicated interactions is essential for developing personalized interventions to delay onset, reduce severity, and slow AD progression.

show abstract

Section: In Uence On Biochemical Pathways and Cellular Processesmentioning

confidence: 99%

Section: In Uence On Biochemical Pathways and Cellular Processesmentioning

confidence: 99%

Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability

Shafi,

Siddiqui

2024

Preprint

View full text Add to dashboard Cite

show abstract

Analysis of the Association of Haplotypes with Alzheimer’s Disease and Mild Cognitive Impairment in the Russian Population

et al. 2020

View full text Add to dashboard Cite

A rare variant in the sortilin-related receptor 1 gene is associated with declined cognitive functions in the elderly

Abstract: The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.

Cited by 2 publications

References 22 publications

Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability

Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability

Analysis of the Association of Haplotypes with Alzheimer’s Disease and Mild Cognitive Impairment in the Russian Population

Contact Info

Product

Resources

About