The relationship between the apolipoprotein E (ApoE) ε4 genotype and an increased risk of developing Alzheimer's disease (AD) has been well established in Caucasians but is less established among other ethnicities. ApoE ε4 has also been associated with several other neurological disorders. Whether ApoΕ4 ε4 is a risk factor for frontotemporal dementia (FTD) remains controversial. This study examined 432 patients with AD, 62 with FTD, and 381 sex- and age-matched controls. The ApoE ε4 allele frequency was significantly increased among patients in the AD and FTD groups compared with controls. The frequency of the ApoΕ ε4 allele was 24.86% in late-onset AD (p < 0.01), 18.02% in early-onset AD (p < 0.01), 16.13% in FTD (p < 0.01), and 7.34% in controls. ApoΕ ε4 prevalence was similar in the FTD and AD groups. The present study suggests that the ApoE ε4 allele is a risk factor for both disorders.

Querfurth HW, LaFerla FM: Alzheimer's disease. N Engl J Med 2010;362:329-344.
Rademakers R, Neumann M, Mackenzie IR: Advances in understanding the molecular basis of frontotemporal dementia. Nat Rev Neurol 2012;8:423-434.
Hirtz D, Thurman DJ, Gwinn-Hardy K, et al: How common are the ‘common' neurologic disorders? Neurology 2007;68:326-337.
Rogers BS, Lippa CF: A clinical approach to early-onset inheritable dementia. Am J Alzheimers Dis Other Demen 2012;27:154-161.
The Lund and Manchester Groups: Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 1994;57:416-418.
Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT; National Institute on Aging; Alzheimer's Association: National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 2012;123:1-11.
Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM; Consortium for Frontotemporal Lobar Degeneration: Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 2007;114:5-22.
Potter H, Wisniewski T: Apolipoprotein E: essential catalyst of the Alzheimer amyloid cascade. Int J Alzheimers Dis 2012;2012:489428.
Verghese PB, Castellano JM, Holtzman DM: Apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurol 2011;10:241-252.
Ward A, Crean S, Mercaldi CJ, Collins JM, Boyd D, Cook MN, Arrighi HM: Prevalence of apolipoprotein E4 genotype and homozygotes (APOE e4/4) among patients diagnosed with Alzheimer's disease: a systematic review and meta-analysis. Neuroepidemiology 2012;38:1-17.
Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R, Myers R, Pericak-Vance M, Risch N, van Duijn C: 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;278:1349-1356.
Corder EH, Saunders AM, Strittmatter WJ, Schmechel D, 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.
Ji Y, Urakami K, Adachi Y, Maeda M, Isoe K, Nakashima K: Apolipoprotein E polymorphism in patients with Alzheimer's disease, vascular dementia and ischemic cerebrovascular disease. Dement Geriatr Cogn Disord 1998;9:243-245.
Tang M, Stern Y, Marder K, Bell K, Gurland B, Lantigua R, Andrews H, Feng L, Tycko B, Mayeux R: The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA 1998;279:751-755.
Myers R, Schaefer E, Wilson P, D'Agostino R, Ordovas J, Espino A, Au R, White R, Knoefel J, Cobb J, McNulty K, Beiser A, Wolf P: Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study. Neurology 1996;46:673-677.
Gureje O, Ogunniyi A, Baiyewu O, Price B, Unverzagt F, Evans R, Smith-Gamble V, Lane K, Gao S, Hall K, Hendrie H, Murrell J: APOE epsilon4 is not associated with Alzheimer's disease in elderly Nigerians. Ann Neurol 2006;59:182-185.
Hendrie H, Murrell J, Gao S, Unverzagt F, Ogunniyi A, Hall K: International studies in dementia with particular emphasis on populations of African origin. Alzheimer Dis Assoc Disord 2006;20:S42-S46.
Gustafson L, Abrahamson M, Grubb A, Nilsson K, Fex G: Apolipoprotein-E genotyping in Alzheimer's disease and frontotemporal dementia. Dement Geriatr Cogn Disord 1997;8:240-224.
Stevens M, van Duijn CM, de Knijff P, van Broeckhoven C, Heutink P, Oostra BA, Niermeijer MF, van Swieten JC: Apolipoprotein E gene and sporadic frontal lobe dementia. Neurology 1997;48:1526-1529.
Seripa D, Bizzarro A, Panza F, Acciarri A, Pellegrini F, Pilotto A, Masullo C: The APOE gene locus in frontotemporal dementia and primary progressive aphasia. Arch Neurol 2011;68:622-628.
Minthon L, Hesse C, Sjögren M, Englund E, Gustafson L, Blennow K: The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease. Neurosci Lett 1997;226:65-67.
Geschwind D, Karrim J, Nelson SF, Miller B: The apolipoprotein E epsilon4 allele is not a significant risk factor for frontotemporal dementia. Ann Neurol 1998;44:134-138.
Pickering-Brown SM, Owen F, Isaacs A, et al: Apolipoprotein E epsilon4 allele has no effect on age at onset or duration of disease in cases of frontotemporal dementia with pick- or microvacuolar-type histology. Exp Neurol 2000;163:452-456.
Kowalska A, Asada T, Arima K, Kumakiri C, Kozubski W, Takahashi K, Tabira T: Genetic analysis in patients with familial and sporadic frontotemporal dementia: two tau mutations in only familial cases and no association with apolipoprotein epsilon4. Dement Geriatr Cogn Disord 2001;12:387-392.
Verpillat P, Camuzat A, Hannequin D, Thomas-Anterion C, Puel M, Belliard S, Dubois B, Didic M, Lacomblez L, Moreaud O, Golfier V, Campion D, Brice A, Clerget-Darpoux F: Apolipoprotein E gene in frontotemporal dementia: an association and meta-analysis. Eur J Hum Genet 2002;10:399-405.
Ren RJ, Huang Y, Xu G, Li CB, Cheng Q, Chen SD, Wang G: History, present, and progress of frontotemporal dementia in China: a systematic review. Int J Alzheimers Dis 2012;2012;587215.
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.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders; ed 4, Text Revision. Washington, American Psychiatric Association, 2000, pp 157-158.
Rosen WE, Terry RD, Fuld PA, Katzman R, Peck A: Pathological verification of ischemic score in differentiation of dementias. Ann Neurol 1980;8:486-488.
Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF: Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546-1554.
Cairns NJ, Bigio EH, Mackenzie IR, Neumann M, Lee VM, Hatanpaa KJ, White CL 3rd, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DM; Consortium for Frontotemporal Lobar Degeneration: Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 2007;114:5-22.
Zhang ZX, Hong X, Li H, et al: The Mini-Mental State Examination in a population aged 55 years and over in urban and rural areas of Beijing (in Chinese). Zhonghua Shen Jing Ge Za Zhi 1999;32:149-153.
Wenham PR, Price WH, Blandell G: Apolipoprotein E genotyping by one-stage PCR. Lancet 1991;337:1158-1159.
Kobayahsi S, Tateno M, Park T, Utsumi K, Sohma H, Ito Y, Kokai Y, Saito T: Apolipoprotein E4 frequencies in a Japanese population with Alzheimer's disease and dementia with Lewy bodies. PLoS One 2011;6:e18569.
Zhang JG, Dong, XZ, Yang WJ, Lu Q, He L: Population distributions of allele frequency of apolipoprotein E by age and gender in Han Chinese. Zhongguo Yao Li Xue Bao 1999;20:218-222.
Fabre SF, Forsell C, Viitanen M, Sjögren M, Wallin A, Blenno K, Blomberg M, Andersen C, Wahlund Lo, Lannfelt L: Clinic-based cases with frontotemporal dementia show increased cerebrospinal fluid tau and high apolipoprotein E epsilon 4 frequency, but no tau gene mutations. Exp Neurol 2001;168:413-418.
Crean S, Ward A, Mercaldi CJ, Collins JM, Cook MN, Baker NL, Arrighi M: Apolipoprotein E epsilon 4 prevalence in Alzheimer's disease patients varies across global populations: a systematic literature review and meta-analysis. Dement Geriatr Cogn Disord 2011;31:20-30.
Wu YN, Zhang JW, Zhang ZX, Qu ZM, Chen D: An association analysis of apolipoprotein E genotypes with Alzheimer's disease in Chinese population. Zhongguo Yi Xue Ke Xue Yan Xue Bao 2001;23:450-454.
Helisalmi S, Linnaranta K, Lehtovirta M, Mannermaa A, Heinonen O, Ryynanen M, Riekkinen P Sr, Soininen H: Apolipoprotein E polymorphism in patients with different neurodegenerative disorders. Neurosci Lett 1996;66:184-188.
Götz J, Ittner LM, Schonrock N: Alzheimer's disease and frontotemporal dementia: prospects of a tailored therapy? Med J Aust 2006;185:381-384.
Golde TE, Dickson D, Hutton M: Filling the gaps in the abeta cascade hypothesis of Alzheimer's disease. Curr Alzheimer Res 2006;3:421-430.
Brecht WJ, Harris FM, Chang S, Tesseur I, Yu GQ, Xu Z, Dee Fish J, Wyss-Coray T, Buttini M, Mucke L, Mahley RW, Huang Y: Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J Neurosci 2004;24:2527-2534.
Strittmatter WJ, Weisgraber KH, Goedert M, Saunders AM, Huang D, Corder EH, Dong L, Jakes R, Alberts MJ, Gilbert JR, Han S, Hulette C, Einstein G, Schmechel DE, Pericak-Vance, Rosese AD: Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exp Neurol 1994;125:163-171.
Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ, et al: Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993;43:1467-1472.
Brion JP: The neurobiology of Alzheimer's disease. Acta Clin Belg 1996;51:80-90.
Castellano JM, Kim J, Stewart FR, Jiang H, DeMattos RB, Patterson BW, Fagan AM, Morris JC, Mawuenyega KG, Cruchaga C, Goate AM, Bales KR, Paul SM, Bateman RJ, Holtzman DM: Human apoE isoforms differentially regulate brain amyloid-β peptide clearance. Sci Transl Med 2011;3:89ra57.
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