Can we blame the increase in Alzheimer’s on our genes?
Over 200 genes so far have been identified that influence the risk of Alzheimer’s – so is this disease a consequence of our genetics or a mismatch of our genes with our environment?
Whilst the rare ‘early onset familial Alzheimer’s’ is strongly linked to genetics; the more prevalent ‘late onset’ form involves multiple risk factors and risk genes – it is a new disease of our diet and lifestyle and the way these factors interact with our genes. One hundred years ago Alzheimer’s was not a significant problem and our genes have not changed since then. For example, in the US there were about 200,000 people with Alzheimer’s in 1910, equivalent to about 0.2% of the population; in 2015 it was around 7 million which is 2.2% of the population.
The gene variant with the greatest known influence on the risk of developing Late Onset Alzheimer’s is called ApoE4 (Apolipoprotein E4). This is the gene that James Watson, the co-discoverer of DNA, did not want to learn about when having his entire genome sequenced.
About one quarter of the general population has one copy of the ApoE4 variant. This increases their lifetime risk of developing Alzheimer’s by up to four times. About two per cent of the population has two copies of ApoE4, i.e. one from each parent. This increases the risk of developing Alzheimer’s by about ten times or more.
What is the mechanism by which ApoE4 is involved in Alzheimer’s?
The mechanisms by which ApoE4 increases risk were described in a paper by Professor Bredesen’s team in 2016. It explained that ApoE4 functions as a transcription factor; a transcription factor is a protein that binds to specific DNA sequences controlling the rate of transcription of genetic information from DNA to messenger RNA. The paper states:
“ApoE4 undergoes nuclear translocation …… and functions as a transcription factor …… the ApoE4 binding sites include ~1700 gene promoter regions. The genes associated with these promoters provide new insight into the mechanism by which Alzheimer’s risk is conferred by ApoE4 because they include genes associated with trophic support, programmed cell death, microtubule disassembly, synaptic function, sirtuins and aging and insulin resistance, all processes that have been implicated in Alzheimer’s disease pathogenesis.” Theendakara et al 2016.
In fact of these 1700 genes, 76 have been found to have a role in Alzheimer’s pathology! That said, a person with the high risk variant may not get Alzheimer’s and conversely one lacking the variant may still get the disease. ApoE4 carriers may have their risk of developing Alzheimer’s disease modified by mutations elsewhere in their genomes. Among the other genes that have been found to be relevant in increasing risk are genes that affect beta-amyloid clearance, cholesterol and lipid metabolism, neurogenesis, blood coagulation, thyroid health, gluten tolerance, microglia function, mitochondrial health and methylation, to name a few.
This talk will (briefly) discuss some of the key genes that can increase the risk of Alzheimer’s and how Professor Bredesen and others are using nutrition, lifestyle and a functional medicine approach, to prevent and reverse cognitive decline.
Alzheimer’s Society (2012) – Genetics of Alzheimers factsheet.
Alzforum (2009) – Early ApoE4 memory effects, but do you really want to know?
Theendakara V et al (2016) – Direct Transcriptional Effects of Apolipoprotein E. The Journal of Neuroscience, January 2016
DOI: 10.1523/JNEUROSCI. 3562-15.2016