• Mayuri Vaish

Genetics and Alzheimer's?

Updated: Dec 12, 2018

Yes, there has been prior research linking DNA evidence to amyloid plaque buildup, a hallmark for Alzheimer’s Disease and neurodegeneration.


One such candidate was the Amyloid Protein Precursor (APP) gene, located on chromosome 21 of the human genome.[1]. Prior research has found a point mutation in the APP gene within subsets of individuals with Alzheimer’s[2]. However, later research showed that such mutations only contributed to a small amount of AD cases[3].


However, other notable genes include PSEN1 and PSEN2 (STM2), on chromosomes 14 and 1 respectively. PSEN1 has shown to account for 50% of the risk of AD as compared to APOE4[4]. For PSEN2, One study revealed that AD-patients contained lower levels of PSEN2 gene expression as compared to healthy controls[5], while another similarly revealed that there were low levels of PSEN2 expression in the brain[6]. Researchers also found a point mutation in PSEN2 among German AD patients[7]: Now, upto 10 different mutations have been found in PSEN2[8]. This evidence suggests that PSEN2, a gene responsible for processing amyloid proteins, can promote amyloid-beta formation if underexpressed[9].


Additionally, the APOE-encoding gene (APOE4 allele) has been correlated with higher risk of late-onset AD[10], due to the interactions with apolipoprotein E with amyloid beta in vitro[11], and this correlation has been proved significant throughout many further studies[12].


Another gene is BACE1, also responsible for amyloid processing[13], and has been shown to promote the development of amyloid-beta, and thus has been a therapeutic target for Alzheimer’s[14].


With regards to tau, since tau is more linked with Parkinson’s there is comparatively less research in relation to AD, but still quite a bit. One example is the tau P310L gene, the overexpression of which promoted protein misfolding, leading to AD-resembling neurodegeneration[15]. Research has also shown that the MAPT gene (which encodes tau protein), where carriers of the MAPT allele have shown to have higher risk of AD than non-carriers[16].


In reality, there are several genes known to implicate AD development. The prevalence and risk for these gene mutations is summarized in the image below:



Here is a very good website I would recommend that provides information on genetic association studies in relation to AD: AlzGene


Lastly, I would like to recommend this amazing review, combining upto 20 years of research on the role of genetics in Alzheimer’s. What a read! ScienceDirect


In conclusion, yes. The effects of genes aren’t necessarily due to external ‘damage’, they largely comprise of mutations or have lower/higher secretion. However, these mentioned genetic changes can also be brought about by ‘DNA damage’ such as exposure to radiation, which promotes the onset of mutations by interfering with DNA molecular activity. I mentioned evidence behind the role of several genes in abnormal amyloid-beta production, and there is a large body of research discussing the interactions of a variety of other genes.