Background: Poly-T repeat lengths of rs10524523 in TOMM40 together with APOE polymorphism have been reported to affect the risk of late-onset Alzheimer's disease (LOAD) and the age of onset (AOO). Objective: To explore whether the AOO and cerebrospinal fluid biomarkers Aβ42, total tau and phosphorylated tau are associated with different repeat lengths. Methods: We conducted both the fragment and sequencing analysis of rs10524523 in 336 LOAD patients with a known APOE genotype. Results: AOO and Aβ42 levels associated significantly with certain poly-T repeat lengths of rs10524523 in LOAD patients encompassing APOE 34/44 genotype. Conclusion: We conclude that the poly-T repeat associations of rs10524523 in TOMM40 reflect the APOE ε4-dependent association in LOAD.

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 1993;261:921-923.
Roses AD, Lutz MW, Amrine-Madsen H, Saunders AM, Crenshaw DG, Sundseth SS, Huentelman MJ, Welsh-Bohmer KA, Reiman EM: A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease. Pharmacogenomics J 2010;10:375-384.
Lutz MW, Crenshaw DG, Saunders AM, Roses AD: Genetic variation at a single locus and age of onset for Alzheimer's disease. Alzheimers Dement 2010;6:125-131.
Linnertz C, Saunders AM, Lutz MW, Crenshaw DM, Grossman I, Burns DK, Whitfield KE, Hauser MA, McCarthy JJ, Ulmer M, Allingham R, Welsh-Bohmer KA, Roses AD, Chiba-Falek O: Characterization of the poly-T variant in the TOMM40 gene in diverse populations. PLoS One 2012;7:e30994.
Gabriel K, Egan B, Lithgow T: Tom40, the import channel of the mitochondrial outer membrane, plays an active role in sorting imported proteins. EMBO J 2003;22:2380-2386.
Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK: Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J Neurosci 2006;26:9057-9068.
Lehtovirta M, Soininen H, Helisalmi S, Mannermaa A, Helkala EL, Hartikainen P, Hänninen T, Ryynänen M, Riekkinen PJ: Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism. Neurology 1996;46:413-419.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 1994.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.
Ben-Avi L, Durst R, Shpitzen S, Leitersdorf E, Meiner V: Apolipoprotein E genotyping: accurate, simple, high throughput method using ABI Prism SNaPshot Multiplex System. J Alzheimers Dis 2004;6:497-501.
Maruszak A, Pepłońska B, Safranow K, Chodakowska-Żebrowska M, Barcikowska M, Żekanowski C: TOMM40 rs10524523 polymorphism's role in late-onset Alzheimer's disease and in longevity. J Alzheimers Dis 2012;28:309-322.
Chu SH, Roeder K, Ferrell RE, Devlin B, DeMichele-Sweet MA, Kamboh MI, Lopez OL, Sweet RA: TOMM40 poly-T repeat lengths, age of onset and psychosis risk in Alzheimer disease. Neurobiol Aging 2011;32:2328.
Bernardi L, Gallo M, Anfossi M, Conidi ME, Colao R, Puccio G, Cursio SA, Frangipane F, Clodomiro A, Mirabelli M, Vasso F, Smirne N, Di Lorenzo R, Maletta R, Bruni AC: Role of TOMM40 rs10524523 polymorphism in onset of Alzheimer's disease caused by the PSEN1 M146L mutation. J Alzheimers Dis 2013;37:285-289.
Cruchaga C, Nowotny P, Kauwe JS, Ridge PG, Mayo K, Bertelsen S, Hinrichs A, Fagan AM, Holtzman DM, Morris JC, Goate AM; for the Alzheimer's Disease Neuroimaging Initiative: Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease. Arch Neurol 2011;68:1013-1019.
Jun G, Vardarajan BN, Buros J, Yu C-E, Hawk MV, Dombroski BA, Crane PK, Larson EB, Mayeux R, Haines JL, Lunetta KL, Pericak-Vance MA, Schellenberg GD, Farrer LA: Comprehensive search for Alzheimer disease susceptibility loci in the APOE region. Arch Neurol 2012;69:1270-1279.
Bekris LM, Lutz F, Yu C-E: Functional analysis of APOE locus genetic variation implicates regional enhancers in the regulation of both TOMM40 and APOE. J Hum Genet 2012;57:18-25.
Linnertz C, Anderson L, Gottschalk W, Crenshaw D, Lutz MW, Allen J, Saith S, Mihovilovic M, Burke JR, Welsh-Bohmer KA, Roses AD, Chiba-Falek O: The cis-regulatory effect of an Alzheimer's disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes. Alzheimers Dement 2014;10:541-551.
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