Genetics

Genes are not destiny. They are programs that must be "activated" to affect change.

Genetics do NOT account for the majority of Alzheimer's risk. Genetics may determine if AD happens, but environmental factors determine WHEN.

Age is still the #1 factor in developing Alzheimer’s disease. The risk of Alzheimer’s at age 65 is about 2%. The risk doubles every 5 years after 65, with the average risk peaking at 33% after age 85. (alz.org)

The lifetime risk of Alzheimers for someone without ApoE4 is 9%. Having the ApoE4 gene (one copy or two) lowers the age of onset and increases the risk of development. The lifetime risk for individuals with E4/E4 may be as high as 25% for males and 45% for females. (alzdiscovery)(labcorp genetic testing)

30-50% of all individuals with late onset Alzheimer’s do not have any ApoE4 alleles. (labcorp genetic testing) ApoE4 seems to be more genetically deterministic in women, possibly due to higher estrogen levels, iron accumulation after menopause, and/or birth/family burden. (science, 2014)

ApoE4 codes for lipid transport genes. Carriers of the ApoE4 allele show less efficient glucose uptake and usage in the brain (Wu, 2018) ApoE4 carriers also have leakier blood brain barriers. (Winkler, 2014)(Nishitsuji, 2011)(Carmeliet, 2012)

Among Nigerians and elderly costa ricans, ApoE4 was found to be PROTECTIVE against Alzheimer's disease. However, these were very small studies and most likely did not involve "western" diets or environments. (Guereje, 2006) (Valerio, 2014)

Among 14,435 Swedish monozygotic twin pairs, there was a 60% concordance with developing Alzheimer’s and when both twins did have AD, there could be up to 7 years difference between the age of onset. (Gatz, 2005)

Among 13,888 Finnish monozygotic twin pairs, there was an 18% concordance for Alzheimer’s and the age of onset differed up to 15 years. (Raiha, 1996)

TOMM40 is another gene showing twice the risk of Alzheimer's, but it is near ApoE4 on chromosome 19 and may show up as a risk because of gene linkage.

The early onset genes (PSEN1, PSEN2, APP) are extremely rare and known to exist in only 20 families. There should be direct parent linkage with these genes. (NIH genetic fact sheet)