APOE4 allele in north Indian elderly patients with dementia or late onset depression-a multiple-disease case control study

Document Type : Original article

Authors

1 Department of Geriatric Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

2 Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

3 Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India

Abstract

The objective of the study was to analyze the frequency of APOE4 allele in elderly patients with Alzheimer’s or vascular dementia or depression; compare these to age/sex matched controls; compare the results with established literature and highlight new findings.A single center, multiple disease, case-control study was performed with three case groups- probable AD patients (n=36), vascular dementia patients (n=29) and depression patients (n=20) and with a control group (n=32). APOE genotyping was performed in whole blood samples collected from patients and controls by restriction isotyping using the enzymes AflIII and HaeII. There was significant difference in frequency distribution of E4 allele between the AD (12/72; 16.7%) and control groups (3/64; 4.7%) (P=0.03). However, no significant difference was found in any of the other comparisons. The current study demonstrates absence of a significant association between APOE4 positivity and presence of late-onset depression in the north Indian elderly and reinforces the higher APOE4 prevalence in LOAD patients but not in VD patients. It is the first study of its kind from the northern part of India involving multiple disease groups and lays the framework for larger cohort studies.

Keywords

References

1. Enache D, Winblad B, Aarsland D. Depression in dementia: epidemiology, mechanisms, and treatment. Curr Opin Psychiatry 2011;24:461-472.
2. Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P. Alzheimer’s disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurol 2008;7:812-826.
3. Dubois B, Feldman HH, Jacova C, Cummings JL, DeKosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010;9:1118-1127.
4. Brickell KL, Steinbart EJ, Rumbaugh M, Payami H, Schellenberg GD, Van Deerlin V, Yuan W, Bird TD. Early-onset Alzheimer disease in families with late-onset Alzheimer disease. Arch Neurol 2006;63:1307-1311.
5. Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 1988;240:622-630.
6. Das HK, McPherson J, Bruns GAP, Karathanasis SK, Breslow JL. Isolation, characterization and mapping to chromosome 19 of the human apolipoprotein E gene. J Biol Chem 1985; 260:6240-6247.
7. Nagy ZS, Esiri MM, Jobst KA, Johnston C, Litchfield S, Sim E, Smith AD. Influence of the apolipoprotein E genotype on amyloid deposition and neurofibrillary tangle formation in Alzheimer’s disease. Neuroscience 1995;69:757-761.
8. Ganguli M, Chandra V, Kamboh MI, Johnston JM, Dodge HH, Thelma BK, Juyal RC, Pandav R, Belle SH, DeKosky ST. Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US cross-national dementia study. Arch Neurol 2000;57:824-830.
9. Kota LN, Shankarappa BM, Shivakumar P, Sadanand S, Bagepally BS, Krishnappa SB, Purushottam M, Sivakumar PT, Jain S, Varghese M, Bharath S. Dementia and diabetes mellitus: association with apolipoprotein e4 polymorphism from a hospital in southern India. Int J Alzheimer’s Dis 2012; 2012:702972.
10. Ritchie K, Lovestone S. The dementias. Lancet 2002;360:1759-1766.
11. Orth M, Bellosta S. Cholesterol: its regulation and role in central nervous system disorders. Cholesterol 2012;2012:292598.
12. Üstün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year 2000. Br J Psychiatry 2004;184:386-392.
13. Teri L. Behavior and caregiver burden: Behavioral problems in patients with Alzheimer disease and its association with caregiver distress. Alzheimer Dis Assoc Disord 1997;11: S35-38.
14. Steffens DC, Plassman BL, Helms MJ, Welsh-Bohmer KA, Saunders AM, Breitner JCS. A twin study of late-onset depression and apolipoprotein E ε4 as risk factors for Alzheimer’s disease. Biol Psychiatry 1997;41:851-856.
15. Sureshkumar R, Bharath S, Jain S, Prakash O, Purushottam M, Thennarasu K, Mukherjee O, Sivakumar PT, Varghese M. ApoE4 and late onset depression in Indian population. J Affect Disord 2012;136:244-248.
16. Sambrook J, Russell DW. Purification of nucleic acids by extraction with phenol: chloroform. CSH Protoc 2006;2006:pdb-prot4455.
17. Ganguli M, Ratcliff G, Chandra V, Sharma S, Gilby J, Pandav R, Belle S, Ryan C, Baker C, Seaberg E. Dekosky S. A Hindi version of the MMSE: the development of a cognitive screening instrument for a largely illiterate rural elderly population in India. Int J Geriatr Psychiatry 1995;10:367-377.
18. Tsolaki M, Iakovidou V, Navrozidou H, Aminta M, Pantazi T, Kazis A. Hindi Mental State Examination (HMSE) as a screening test for illiterate demented patients. Int J Geriatr Psychiatry 2000;15:662-664.
19. Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1982;17:37-49.
20. Zivelin A, Rosenberg N, Peretz H, Amit Y, Kornbrot N, Seligsohn U. Improved method for genotyping apolipoprotein E polymorphisms by a PCR-based assay simultaneously utilizing two distinct restriction enzymes. Clin Chem 1997;43:1657-1659.
21. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, Van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA 1997; 278:1349-1356.
22. Rohn TT. Is apolipoprotein E4 an important risk factor for vascular dementia? Int J Clin Exp Pathol 2014;7:3504-3511.
23. Traykov L, Bayle AC, Latour F, Lenoir H, Seux ML, Hanon O, Péquignot R, Bert P, Moulin F, Cantegreil I, Wenisch E, Batouche F, Mehrabian S, Rotrou JD, Rigaud AS. Apolipoprotein E ε4 allele frequency in elderly depressed patients with and without cerebrovascular disease. J Neurol Sci 2007;257:280-283.
24. Rigaud AS, Traykov L, Caputo L, Coste J, Latour F, Couderc R, Moulin F, Boller F, Forette F. Association of the apolipoprotein E epsilon4 allele with late-onset depression. Neuroepidemiology 2001;20:268-272.
25. Kitzlerová E, Fišar Z, Lelková P, Jirák R, Zvěřová M, Hroudová J, Manukyan A, Martásek P, Raboch J. Interactions among polymorphisms of susceptibility loci for Alzheimer’s disease or depressive disorder. Med Sci Monit 2018;24:2599-2619.
26. Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry 2013;202:329-335.

Files

Share

How to cite

Statistics