Sorting Out the Role of the in Alzheimer's Disease

Overview

Journal J Alzheimers Dis Rep

Publisher IOS Press

Date 2020 Jun 27

PMID 32587946

Citations 13

Authors

Karissa Barthelson

Morgan Newman

Michael Lardelli

Affiliations

Soon will be listed here.

Abstract

encodes a large, multi-domain containing, membrane-bound receptor involved in endosomal sorting of proteins between the trans-Golgi network, endosomes and the plasma membrane. It is genetically associated with Alzheimer's disease (AD), the most common form of dementia. is a unique gene in AD, as it appears to show strong associations with the common, late-onset, sporadic form of AD and the rare, early-onset familial form of AD. Here, we review the genetics of in AD and discuss potential roles it could play in AD pathogenesis.

Citing Articles

Genetic Markers of Postmortem Brain Iron.

Cornelis M, Fazlollahi A, Bennett D, Schneider J, Ayton S J Neurochem. 2025; 169(2):e16309.

PMID: 39918201 PMC: 11804167. DOI: 10.1111/jnc.16309.

Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer's Disease.

Kim Y, Ha T, Lee M, Chang K Int J Biol Sci. 2025; 21(3):1014-1031.

PMID: 39897039 PMC: 11781173. DOI: 10.7150/ijbs.103028.

Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.

Sokolowski E, Kursawe R, Selvam V, Bhuiyan R, Thibodeau A, Zhao C Cell Metab. 2024; 36(11):2468-2488.e7.

PMID: 39383866 PMC: 11798411. DOI: 10.1016/j.cmet.2024.09.006.

Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer's Disease.

Oviya I, Sankar D, Manoharan S, Prabahar A, Raja K Genes (Basel). 2024; 15(5).

PMID: 38790243 PMC: 11121575. DOI: 10.3390/genes15050614.

Systematic Analysis of Biological Processes Reveals Gene Co-expression Modules Driving Pathway Dysregulation in Alzheimer's Disease.

Adeoye T, Shah S, Ullah G bioRxiv. 2024; .

PMID: 38559218 PMC: 10980062. DOI: 10.1101/2024.03.15.585267.

References

Area-Gomez E, de Groof A, Boldogh I, Bird T, Gibson G, Koehler C . Presenilins are enriched in endoplasmic reticulum membranes associated with mitochondria. Am J Pathol. 2009; 175(5):1810-6. PMC: 2774047. DOI: 10.2353/ajpath.2009.090219. View

Lovell M, ROBERTSON J, Teesdale W, Campbell J, Markesbery W . Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci. 1998; 158(1):47-52. DOI: 10.1016/s0022-510x(98)00092-6. View

Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B . A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat Genet. 1992; 1(5):345-7. DOI: 10.1038/ng0892-345. View

Ciarlo E, Massone S, Penna I, Nizzari M, Gigoni A, Dieci G . An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples. Dis Model Mech. 2012; 6(2):424-33. PMC: 3597024. DOI: 10.1242/dmm.009761. View

Wong B, Tsatsanis A, Lim L, Adlard P, Bush A, Duce J . β-Amyloid precursor protein does not possess ferroxidase activity but does stabilize the cell surface ferrous iron exporter ferroportin. PLoS One. 2014; 9(12):e114174. PMC: 4252103. DOI: 10.1371/journal.pone.0114174. View

Yajima R, Tokutake T, Koyama A, Kasuga K, Tezuka T, Nishizawa M . ApoE-isoform-dependent cellular uptake of amyloid-β is mediated by lipoprotein receptor LR11/SorLA. Biochem Biophys Res Commun. 2014; 456(1):482-8. DOI: 10.1016/j.bbrc.2014.11.111. View

Blechingberg J, Poulsen A, Kjolby M, Monti G, Allen M, Ivarsen A . An alternative transcript of the Alzheimer's disease risk gene SORL1 encodes a truncated receptor. Neurobiol Aging. 2018; 71:266.e11-266.e24. PMC: 6769419. DOI: 10.1016/j.neurobiolaging.2018.06.021. View

Sannerud R, Esselens C, Ejsmont P, Mattera R, Rochin L, Tharkeshwar A . Restricted Location of PSEN2/γ-Secretase Determines Substrate Specificity and Generates an Intracellular Aβ Pool. Cell. 2016; 166(1):193-208. PMC: 7439524. DOI: 10.1016/j.cell.2016.05.020. View

Lambert J, Ibrahim-Verbaas C, Harold D, Naj A, Sims R, Bellenguez C . Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013; 45(12):1452-8. PMC: 3896259. DOI: 10.1038/ng.2802. View

10.

Richardson D, Ponka P . The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta. 1997; 1331(1):1-40. DOI: 10.1016/s0304-4157(96)00014-7. View

11.

Huang T, Zhao Y, Li X, Wang X, Tseng I, Thompson R . SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein. J Neurosci. 2016; 36(30):7996-8011. PMC: 4961782. DOI: 10.1523/JNEUROSCI.0206-16.2016. View

12.

Scherzer C, Offe K, Gearing M, Rees H, Fang G, Heilman C . Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Arch Neurol. 2004; 61(8):1200-5. DOI: 10.1001/archneur.61.8.1200. View

13.

Nilsen J, Chen S, Irwin R, Iwamoto S, Brinton R . Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function. BMC Neurosci. 2006; 7:74. PMC: 1636062. DOI: 10.1186/1471-2202-7-74. View

14.

Murrell J, Farlow M, Ghetti B, Benson M . A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science. 1991; 254(5028):97-9. DOI: 10.1126/science.1925564. View

15.

Muhammad A, Flores I, Zhang H, Yu R, Staniszewski A, Planel E . Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation. Proc Natl Acad Sci U S A. 2008; 105(20):7327-32. PMC: 2386077. DOI: 10.1073/pnas.0802545105. View

16.

Lee J, McBrayer M, Wolfe D, Haslett L, Kumar A, Sato Y . Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification. Cell Rep. 2015; 12(9):1430-44. PMC: 4558203. DOI: 10.1016/j.celrep.2015.07.050. View

17.

Goate A, Chartier-Harlin M, Mullan M, Brown J, Crawford F, Fidani L . Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 1991; 349(6311):704-6. DOI: 10.1038/349704a0. View

18.

Spoelgen R, von Arnim C, Thomas A, Peltan I, Koker M, Deng A . Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. J Neurosci. 2006; 26(2):418-28. PMC: 6674411. DOI: 10.1523/JNEUROSCI.3882-05.2006. View

19.

Dodson S, Andersen O, Karmali V, Fritz J, Cheng D, Peng J . Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease. J Neurosci. 2008; 28(48):12877-86. PMC: 2669320. DOI: 10.1523/JNEUROSCI.4582-08.2008. View

20.

Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R . Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997; 278(16):1349-56. View