@article {7975,
	title = {Translating Alzheimer{\textquoteright}s disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs.},
	journal = {Neurobiol Aging},
	volume = {74},
	year = {2019},
	month = {2019 Feb},
	pages = {135-146},
	abstract = {<p>The International Genomics of Alzheimer{\textquoteright}s Project (IGAP) is a consortium for characterizing the genetic landscape of Alzheimer{\textquoteright}s disease (AD). The identified and/or confirmed 19 single-nucleotide polymorphisms (SNPs) associated with AD are located on non-coding DNA regions, and their functional impacts on AD are as yet poorly understood. We evaluated the roles of the IGAP SNPs by integrating data from many resources, based on whether the IGAP SNP was (1) a proxy for a coding SNP or (2) associated with altered mRNA transcript levels. For (1), we confirmed that 12 AD-associated coding common SNPs and five nonsynonymous rare variants are in linkage disequilibrium with the IGAP SNPs. For (2), the IGAP SNPs in CELF1 and MS4A6A were associated with expression of their neighboring genes, MYBPC3 and MS4A6A, respectively, in blood. The IGAP SNP in DSG2 was an expression quantitative trait loci (eQTL) for DLGAP1 and NETO1 in the human frontal cortex. The IGAP SNPs in ABCA7, CD2AP, and CD33 each acted as eQTL for AD-associated genes in brain. Our approach for identifying proxies and examining eQTL highlighted potentially impactful, novel gene regulatory phenomena pertinent to the AD phenotype.</p>},
	issn = {1558-1497},
	doi = {10.1016/j.neurobiolaging.2018.10.017},
	author = {Katsumata, Yuriko and Nelson, Peter T and Estus, Steven and Fardo, David W}
}
@article {8396,
	title = {Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene.},
	journal = {J Neuropathol Exp Neurol},
	volume = {79},
	year = {2020},
	month = {2020 01 01},
	pages = {3-21},
	abstract = {<p>We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n = 119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex. In a separate replication cohort of autopsied subjects (n = 173), more pTau pathology was again observed in subjects with longer VNTR regions (p = 0.031). Unlike MUC6, AP2A2 is highly expressed in human brain. AP2A2 expression was lower in a subset analysis of brain samples from persons with longer versus shorter VNTR regions (p = 0.014 normalizing with AP2B1 expression). Double-label immunofluorescence studies showed that AP2A2 protein often colocalized with neurofibrillary tangles in LOAD but was not colocalized with pTau proteinopathy in progressive supranuclear palsy, or with TDP-43 proteinopathy. In summary, polymorphism in a repeat-rich region near AP2A2 was associated with neocortical pTau proteinopathy (because of the unique repeats, prior genome-wide association studies were probably unable to detect this association), and AP2A2 was often colocalized with neurofibrillary tangles in LOAD.</p>},
	keywords = {Adaptor Protein Complex 2, Adaptor Protein Complex alpha Subunits, Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Cohort Studies, Female, Genome-Wide Association Study, Genotype, Humans, Male, Minisatellite Repeats, Mucin-6, Neurofibrillary Tangles, Polymorphism, Genetic, Polymorphism, Single Nucleotide, TDP-43 Proteinopathies},
	issn = {1554-6578},
	doi = {10.1093/jnen/nlz116},
	author = {Katsumata, Yuriko and Fardo, David W and Bachstetter, Adam D and Artiushin, Sergey C and Wang, Wang-Xia and Wei, Angela and Brzezinski, Lena J and Nelson, Bela G and Huang, Qingwei and Abner, Erin L and Anderson, Sonya and Patel, Indumati and Shaw, Benjamin C and Price, Douglas A and Niedowicz, Dana M and Wilcock, Donna W and Jicha, Gregory A and Neltner, Janna H and Van Eldik, Linda J and Estus, Steven and Nelson, Peter T}
}
