The genetic risk for Alzheimer’s Disease (AD) is as high as 79%. Here are some frequently mentioned gene names, along with some common terms. For early-onset familial AD, the clear causative genes are: 1. amyloid precursor protein (APP); 2. progeria-1 (PSEN1); 3. progeria-2 (PSEN2). Late onset familial dementia is associated with Apolipoprotein E (ApoE) gene polymorphism. The risk of AD is 12-fold higher in ε4 allele purets than in those with the ε4 allele; those with one ε4 allele are two to three times more likely to have the allele; it is involved in the regulation of phospholipid and cholesterol endostasis, synaptic plasticity, neuroinflammation, amyloid metabolism, neurogenic fiber tangles, and apoptotic processes. Late onset familial dementia may also be associated with other genes, as detailed below2. 2. GWAS studies and more genes GWAS, or genome-wide association studies, extract DNA from tissue cells, read millions of DNA sequences on a gene chip, then read the chip sequences into a computer, and finally detect
Genes associated with patients with late-onset familial AD include: (1) CLU: an important apolipoprotein cofactor with increased expression in affected cortical sites, often in senile plaques and cerebrospinal fluid, which decreases intracerebral Aβ by increasing neuronal cell endocytosis or transport across the blood-brain barrier
content and thus inhibits complement activation. (2) PICALM, B1N1: are lattice-protein complexes encoding phosphatidylinositol binding, both involved in lattice-protein-mediated endocytosis and Aβ
production and release, transport of macromolecules such as proteins and lipids, and mediating the fusion of neurotransmitters with presynaptic membranes. (3) CR1: associated with acquired immunity, it is a negative regulator of complement cascade reaction and can inhibit synaptic ablation. 3. Emphasis on controllable factors Besides genetics, many factors can also affect disease, health and survival life span, and these factors are under our control. We list them in the chart below.