@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}
}
